Levodopa Versus Levodopa Sparing in Early Parkinson´s Disease: Can we Meet Halfway?

ABSTRACT Monotherapy is the recommended initial treatment for early Parkinson´s disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson´s disease.

Preparation modification strategies for clinical treatment drugs of Parkinson's disease / 药学学报

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Effects of low-frequency and high-frequency repetitive transcranial magnetic stimulation combined with levodopa and benserazide hydrochloride on mild cognitive impairment in patients with Parkinson disease / 中华行为医学与脑科学杂志

Objective:To investigate the effects of low-frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) combined with levodopa and benserazide hydrochloride on mild cognitive impairment in patients with Parkinson disease (PD).Methods:Totally 90 PD patients with mild cognitive impairment who visited from January 2020 to June 2022 were included , and they were divided into a simple drug group ( n=30), drug+ low-frequency group ( n=30), and drug+ high-frequency group ( n=30) according to the order of admission.The patients in the simple drug group were treated with oral levodopa and benserazide hydrochloride, while the patients in drug+ low-frequency and drug+ high-frequency groups were treated with low-frequency or high-frequency rTMS on the basis of oral levodopa and benserazide hydrochloride.Montreal cognitive assessment(MoCA), digital span (DS), Chinese auditory learning test (CALT), the judgment of line orientation test (JLOT) and verbal fluency test (VFT) were used to evaluate the cognitive function of patients before and after 4 weeks of treatment.SPSS 26.0 was used for statistical analysis.The paired t-test was used for intra-group comparison before and after treatment, while one-way ANOVA was used for inter-group comparison. Results:There were no significant differences in MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT, and VFT scores among patients in the simple drug group before and after 4 weeks of treatment( t=-1.157, -0.648, -0.215, -0.290, -0.154, -0.782, -0.960, all P>0.05). After 4 weeks of treatment, MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT scores in drug+ low-frequency group and drug+ high-frequency group were higher than before treatment (drug+ low frequency group: t=-16.357, -11.379, -7.999, -11.805, -16.624, -15.996, -17.241, all P<0.05; drug+ high-frequency group: t=-25.198, -13.971, -13.904, -25.831, -26.382, -20.108, -15.643, all P<0.05). There were no statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups before treatment (all P>0.05). After treatment, there were statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups (simple drug group : (20.37±1.96), (4.37±1.19), (2.80±0.55), (6.93±1.70), (5.17±1.09), (15.50±2.69), (10.73±1.55); drug+ low-frequency group: (23.83±2.32), (5.87±0.94), (3.87±0.73), (9.17±1.74), (8.13±1.50), (20.77±2.19), (13.30±1.73); drug+ high-frequency group: (27.17±1.64), (6.73±1.01), (4.80±0.81), (11.20±2.06), (10.03±1.54), (25.17±3.14), (15.87±2.05)) (all P<0.05). Further analysis showed that both the drug+ low-frequency and drug+ high-frequency groups had higher scores than the simple drug group, and the drug+ high-frequency group had higher scores than the drug+ low-frequency group(all P<0.05). Conclusion:The combination of drug+ low-frequency or drug+ high-frequency rTMS and drug therapy can help improve cognitive function in patients with PD, and the efficacy of drug+ high-frequency rTMS may be more significant, which provides a new therapeutic idea for clinical treatment of patients with PD.

Parkinson's disease and levodopa-induced dyskinesias: a quantitative analysis through 99mTc-TRODAT-1 SPECT imaging of the brain / Doença de Parkinson e discinesias induzidas por levodopa: uma análise quantitativa por meio de imagem cerebral com SPECT 99mTc-TRODAT-1

Abstract Objective: To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD), with and without LID. Materials and Methods: We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson's Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum. Results: The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without. Conclusion: Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.

Resumo Objetivo: Comparar a densidade do transportador de dopamina (DAT) com outros fatores de risco para discinesia induzida pela L-DOPA em pacientes com doença de Parkinson, com e sem discinesias. Materiais e Métodos: Sessenta e sete sujeitos, 23 voluntários saudáveis e 44 pacientes pareados por idade com diferentes graus de gravidade da doença de Parkinson idiopática (29 homens; idade média ± desvio-padrão (DP), 59 ± 7 anos; duração média ± DP dos sintomas, 10 ± 6 anos; H&Y: média ± DP, 2,16 ± 0,65; UPDRS III: média ± DP, 29,74 ± 17,79). Todos os sujeitos realizaram SPECT cerebral com 99mTc-TRODAT-1. Além disso, foram calculadas as taxas de captação específica ou potenciais de ligação no estriado. Resultados: A densidade de DAT do estriado ipsilateral ou contralateral foi menor no grupo doença de Parkinson. As variáveis duração da doença, dosagem de L-DOPA, doses por dia, tempo de duração do efeito da L-DOPA, H&Y e UPDRS III explicaram a ocorrência de discinesia. Adicionalmente, pacientes com discinesia exibiram menor densidade de DAT no estriado ipsilateral ou contralateral e no núcleo caudado do que os pacientes sem discinesia. Conclusão: O presente estudo sugere que a denervação dopaminérgica pré-sináptica na doença de Parkinson está associada ao desenvolvimento de discinesia induzida pela L-DOPA.

Low serum uric acid levels and levodopa-induced dyskinesia in Parkinson's disease / Níveis séricos baixos de ácido úrico e discinesia induzida por levodopa na doença de Parkinson

Abstract Background Levodopa is the most used and effective medication for motor symptoms of Parkinson disease (PD), its long-term use is associated with the appearance of levodopa-induced dyskinesia (LID). Uric acid (UA) is believed to play an important neuroprotective role in PD. Objective To investigate if serum UA levels are related with the presence of LIDs in PD patients. Also, we investigated the associations among UA levels and clinical features of PD. Methods We enrolled 81 PD patients (dyskinesia = 48; no dyskinesia = 33) in the present study. A blood sample was collected to evaluate serum UA levels, clinical evaluation included the following instruments: Montreal Cognitive Assessment (MoCA), Beck Depression Inventory II (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY), and the sub-item 4.1 of MDS-UPDRS IV (score ≥ 1). Additional relevant clinical information was obtained by a clinical questionnaire. Results Serum UA levels were lower in the dyskinesia group when compared with the no dyskinesia group. The same result was found in the UA levels of both men and women. The multivariate analysis showed lower uric acid levels were significantly associated with having dyskinesia (odds ratio [OR] = 0.424; 95% confidence interval [CI]: 0.221-0.746; p= 0.005). Additional analysis verified that serum UA levels are inversely correlated with depressive symptoms, disease duration, MDS-UPDRS IV and time spent with dyskinesia. A positive correlation was found with age at onset of PD symptoms. Conclusions The present study provides a possible role of serum UA levels in LID present in PD patients.

Resumo Antecedentes A levodopa é a medicação mais utilizada e eficaz para os sintomas motores da doença de Parkinson (DP); seu uso a longo prazo está associado ao aparecimento de discinesia induzida por levodopa (LID). Acredita-se que o ácido úrico desempenhe um importante papel neuroprotetor na DP. Objetivo Investigar se os níveis séricos de AU estão relacionados com a presença de LID em pacientes com DP. Além disso, investigamos as associações entre os níveis de AU e as características clínicas da DP. Métodos Foram incluídos 81 pacientes com DP (discinesia = 48; sem discinesia = 33) no presente estudo. Uma amostra de sangue foi coletada para avaliar os níveis séricos de AU, a avaliação clínica incluiu os seguintes instrumentos: Avaliação Cognitiva de Montreal (MoCA), Inventário de Depressão de Beck (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY) e o subitem 4.1 da MDS-UPDRS IV (escore ≥ 1). Informações clínicas relevantes adicionais foram obtidas por meio de um questionário clínico. Resultados Os níveis séricos de AU foram menores no grupo com discinesia quando comparados ao grupo sem discinesia. O mesmo resultado foi encontrado nos níveis de AU de homens e mulheres. A análise multivariada mostrou que níveis mais baixos de ácido úrico foram significativamente associados a ter discinesia (odds ratio [OR] = 0,424; intervalo de confiança (IC) de 95%: 0,221-0,746; p= 0,005). Análises adicionais verificaram que os níveis séricos de AU estão inversamente correlacionados com sintomas depressivos, duração da doença, MDS-UPDRS IV e tempo gasto com discinesia. Uma correlação positiva foi encontrada com a idade de início dos sintomas da DP. Conclusões O presente estudo fornece um possível papel dos níveis séricos de AU na LID presente em pacientes com DP.

Effects of pramipexole combined with levodopa on cognitive and mitochondrial function of rats after global cerebral ischemia-reperfusion injury / 中国康复理论与实践

ObjectiveTo investigate the effects of dopamine receptor agonist pramipexole and levodopa on emotion and cognition, and mitochondrial membrane potential of rats after global cerebral ischemia-reperfusion injury. MethodsA total of 80 male Sprague-Dawley rats were divided into sham group (n = 20), model group (n = 20), pramipexole group (n = 20) and combined group (n = 20). The latter three groups were used to prepare the model of global cerebral ischemia-reperfusion injury with Pulsinelli's four-vessel occlusion. The pramipexole group was intraperitoneally injected pramipexole 0.5 mg/kg once a day, while the combined group was injected levodopa 50 mg/kg and pramipexole 0.5 mg/kg, for 14 days. Five rats in each group were tested with open field test three, seven and 14 days after modeling; five were tested with Y-maze test seven and 14 days after modeling; five were detected mitochondrial membrane potential three, seven and 14 days after modeling; and five were observed under Nissl's staining14 days after modeling. ResultsCompared with the model group, the number of entries into the central zone (P < 0.05), total distance travelled (P < 0.05) and average velocity (P < 0.05) in the open field test increased in the pramipexole and combined groups seven and 14 days after modeling, duration spent in the central zone increased in the pramipexole and combined groups seven days after modeling (P < 0.05); the rate of spontaneous alternation of Y-maze test increased in the pramipexole and combined groups 14 days after modeling (P < 0.05); mitochondrial membrane potential in hippocampus increased in the pramipexole and combined groups seven and 14 days after modeling (P < 0.05), and it was less in the pramipexole group than in the combined group 14 days after modeling (P < 0.05); and the number of surviving neurons in the hippocampal CA1 increased in the pramipexole and combined groups 14 days after modeling (P < 0.05). ConclusionPramipexole may improve emotion and cognition of rats after global cerebral ischemia-reperfusion injury, and it may be helpful for restoring mitochondrial membrane potential as combining with levodopa.

A resting-state MRI-based study on the characteristics of degree centrality of local brain function in patients with levodopa-induced dyskinesias / 中华老年医学杂志

Objective:To investigate the characteristics of regional brain functional centrality(DC)in patients with levodopa-induced dyskinesia(LID)and to explore the pathogenesis of LID.Methods:A total of 33 PD patients with LID(PD-LID), 41 PD patients without LID(PD-nLID)and 37 healthy controls from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study.Differences in DC among the three groups were compared and the correlation between Z-DC values of the brain regions with differences and the scores of the involuntary movement scale(items 1-7)was analyzed.Results:Compared with Controls, PD-LID patients showed increased DC in the right amygdala(extending to the right globus pallidus)(MNI: x=30, y=-3, z=-18, t=4.00, P<0.05 after AlphaSim correction)and in the right postcentral gyrus(MNI: x=57, y=-9, z=39, t=-3.59; MNI: x=42, y=-33, z=57, t=-4.23, P<0.05 after AlphaSim correction)and reduced DC in the right superior parietal lobule(MNI: x=24, y=-51, z=72, t=-3.95, P<0.05 after AlphaSim correction).Compared with the PD-nLID group, the PD-LID group showed increased DC in the right globus pallidus(MNI: x=30, y=-12, z=-3, t=3.09, P<0.05 after AlphaSim correction).DC changes in the right globus pallidus were positively correlated with AIMS score( r=0.482, P=0.004). Conclusions:The enhancement of DC function in the right globus pallidus may be closely related to the onset and severity of LID.

The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

ZHUANG Lixing's Experience in Differentiating and Treating Levodopa-Induced Dyskinesia in Parkinson's Disease / 中医杂志

This paper summarized Professor ZHUANG Lixing's clinical experience in differentiating and treating levodopa-induced dyskinesia （LID） in Parkinson's disease. It is believed that the fundamental pathogenesis of LID lies in the disharmony or malnourishment of tendons and vessels. Based on the clinical manifestations， peak-dose LID is differentiated into two syndromes： syndrome of hyperactive liver yang causing wind and syndrome of deficiency of both liver and kidney. For the syndrome of hyperactive liver yang causing wind， the treatment focuses on calming the liver to stop the wind， and relaxing the tendons to stop tremors. The main prescription used is Zhengan Xifeng Decoction （镇肝熄风汤） with the addition of Shijueming （石决明） and Zhenzhumu （珍珠母）. For the syndrome of deficiency of both liver and kidney， the treatment focuses on nourishing the liver and kidneys， and replenishing yin to stop the wind. The main prescription used is Dabuyin Pills （大补阴丸） with modification. LID in the acoustic phase is differentiated into syndrome of phlegm-damp blocking middle jiao and syndrome of deficiency of both qi and yin. For the syndrome of phlegm-damp blocking middle jiao， the treatment focuses on dissipating phlegm and eliminating dampness， and nurturing tendons and vessels. Wendan Decoction （温胆汤） or Erchen Decoction （二陈汤） with modification is used. For the syndrome of deficiency of both qi and yin， the treatment focuses on replenishing qi and nourishing blood， and nurturing tendons and vessels. The main prescriptions used are Buzhong Yiqi Decoction （补中益气汤） or Bazhen Decoction （八珍汤） or Shenling Baizhu Powder （参苓白术散） with modification. Biphasic LID is differentiated as the Shaoyang pivot disadvantageousness， and the treatment focuses on harmonizing Shaoyang and regulating the pivot. The main prescription used is Xiaochaihu Decoction （小柴胡汤） with modification.

How I treat Parkinson's disease / Como eu trato a doença de Parkinson

ABSTRACT Background: Parkinson's disease (PD) is a complex neurodegenerative condition. Treatment strategies through all stages of disease progression could affect quality of life and influence the development of future complications, making it crucial for the clinician to be on top of the literature. Objective: This paper reviews the current treatment of PD, from early to advanced stages. Methods: A literature review was conducted focusing on the treatment of PD, in the different stages of progression. Results: Every individual with a new diagnosis of PD should be encouraged to start exercising regularly. In the early stage, treatment should focus on using the lowest dose of levodopa or combination therapy that provides maximum functional capacity, and does not increase the risk of complications, such as peak dose dyskinesias and impulse control disorders. At the moderate and advanced stages, motor fluctuations and complications of treatment dominate the picture, making quality of life one important issue. Rehabilitation programs can improve motor symptoms and should be offered to all patients at any stage of disease progression. Conclusion: Many factors need to be considered when deciding on the best treatment strategy for PD, such as disease progression, presence of risk factors for motor and behavioral complications, potential side effects from dopaminergic therapy and phenotypical variabilities. Treatment should focus on functional capacity and quality of life throughout the whole disease course.

RESUMO Antecedentes: A doença de Parkinson (DP) é uma doença neurodegenerativa complexa. As estratégias de tratamento ao longo de todos os estágios da evolução podem influenciar a qualidade de vida e o desenvolvimento de futuras complicações e, portanto, devem ser devidamente conhecidas pelos médicos que assistem o paciente. Objetivo: Neste artigo são revistos os tratamentos atuais para a DP, desde o estágio inicial até os estágios avançados. Métodos: Uma revisão da literatura foi realizada com enfoque em diferentes estágios da doença. Resultados: Todos os pacientes que recebem o diagnóstico de DP devem ser orientados a praticar atividades físicas regularmente. Em fase inicial do tratamento a estratégia consiste em usar doses mínimas de levodopa ou terapias combinadas que propiciem máxima capacidade funcional, que não aumentem o risco de complicações motoras, tais como discinesias induzidas por levodopa, ou não motoras, como transtornos do controle do impulso. Em estágio moderado ou avançado da doença, complicações como flutuações motoras e discinesias tornam-se relevantes e devem ser manejadas adequadamente. Programas de reabilitação devem ser oferecidos para os pacientes em todos os estágios da DP. Conclusões: Vários fatores devem ser considerados ao se escolher a melhor estratégia para o tratamento da DP. Entre eles destacam-se: fatores de risco para o desenvolvimento de complicações motoras e comportamentais, potenciais efeitos colaterais da terapia dopaminérgica e variabilidade fenotípica. O objetivo das estratégias de tratamento ao longo de toda a evolução da doença é a melhoria da capacidade funcional e da qualidade de vida dos pacientes.

Distonías primarias respondedoras a levodopa (DRD): búsqueda sistemática en Latinoamérica / Dopa-responsive dystonia (DRD): systematic search in Latin America

RESUMEN Las distonías que responden a levodopa (DRD, siglas en inglés) abarcan un grupo de distonías primarias, causadas por deficiencias enzimáticas en la vía metabólica de las aminas y, por definición, comparten como característica principal su respuesta favorable y sostenida a levodopa. Existen hasta seis genes asociados a DRD, siendo el gen GCH1 el más frecuentemente involucrado. La presentación típica de esta entidad se caracteriza por su aparición en la niñez, distonía de inicio en miembros inferiores con fluctuación diurna, leve parkinsonismo y respuesta clara a dosis bajas de levodopa. Se incluye una búsqueda sistemática de la literatura con casos de DRD publicados en Latinoamérica.

SUMMARY Dopa-responsive dystonia (DRD) encompasses a heterogenous group of primary dystonias, caused by enzymatic deficiencies across the amines pathway and, by definition, show as their main characteristic a favorable and sustained response to levodopa. There are up to 6 genes associated with DRD, including pathogenic variants of the GCH1 gene as the most frequently involved. The typical presentation of DRD is characterized by start in childhood, lower limb-onset dystonia with daytime fluctuation, mild parkinsonism, and a sustained response to low doses of levodopa. A systematic literature search on DRD reported cases in Latin America is presented.

Experience with the Rehabilitation of Patients with Parkinson's Disease Using Levodopa-Carbidopa Intestinal Gel（LCIG）Treatment for Their Return to Work / The Japanese Journal of Rehabilitation Medicine

Patients with Parkinson's disease (PD) experience difficulties with activities of daily living (ADLs) at workplace and in their social life depending on the extent of disease progression. Because of their disabilities, patients with PD are forced into early retirement compared to other people of their age group. We present our experience with the rehabilitation of three patients with PD using levodopa-carbidopa intestinal gel (LCIG) treatment for their return to work. The rehabilitation program comprised the following three modules：1) evaluating the patients' ability to walk indoor for a short time；2) assessing their standing and sitting positions to enable them to more easily handle a device；and 3) improving their upper limb function, including skilled movements, for operating a device in emergency. Finally, all three patients exhibited improvements in the Timed Up and Go test results and device operation. Two of the patients returned to their former workplace within 10 months of LCIG treatment initiation and the remaining patient found new employment 1 year after treatment commencement.In conclusion, establishing a rational support system that involves rehabilitation programs and information sharing across multiple occupations is essential for the return to work of patients with PD receiving LCIG treatment.

Experience with the Rehabilitation of Patients with Parkinson's Disease Using Levodopa-Carbidopa Intestinal Gel（LCIG）Treatment for Their Return to Work / The Japanese Journal of Rehabilitation Medicine

Patients with Parkinson's disease (PD) experience difficulties with activities of daily living (ADLs) at workplace and in their social life depending on the extent of disease progression. Because of their disabilities, patients with PD are forced into early retirement compared to other people of their age group. We present our experience with the rehabilitation of three patients with PD using levodopa-carbidopa intestinal gel (LCIG) treatment for their return to work. The rehabilitation program comprised the following three modules：1) evaluating the patients' ability to walk indoor for a short time；2) assessing their standing and sitting positions to enable them to more easily handle a device；and 3) improving their upper limb function, including skilled movements, for operating a device in emergency. Finally, all three patients exhibited improvements in the Timed Up and Go test results and device operation. Two of the patients returned to their former workplace within 10 months of LCIG treatment initiation and the remaining patient found new employment 1 year after treatment commencement.In conclusion, establishing a rational support system that involves rehabilitation programs and information sharing across multiple occupations is essential for the return to work of patients with PD receiving LCIG treatment.

Effect of medication withdrawal on pain in Parkinson's disease patients - an observational study based on a sample of patients without antiparkinsonian medications

SUMMARY OBJECTIVES: To assess the effect of withdrawal of the antiparkinsonian drug regimen administration on patients with PD and its relation to pain. METHODS: The sample included 22 men and 12 women who were candidates for neurosurgery to control motor signs and symptoms treated with L-dopa as a drug, alone or in combination with others (Cholinergic Antagonists; Dopamine Agents). All of them were examined at two different moments, with and without medication, and analyzed for painful symptoms. The Hoehn and Yahr scale was used for functional staging of the disease. Pain intensity was assessed by using the numerical verbal scale. RESULTS: The mean pain intensity among those on medication {2.17±0.39 (SE)} was significantly lower than in the abstinence group {4.2±0.59 (SE), p=0.006, Wilcoxon}, which corresponded to the increase in the total functional staging score from 93 to 111, respectively. CONCLUSION: The interruption of the administration of specific medications in patients with Parkinson's disease caused, or increased the intensity of, painful discomfort correlated with the intensity of functional impairment. This effect was also observed in women, but it was statistically relevant only for men. The results suggest that pain may be a "red flag" that points to the need for a therapeutic drug review when its presence or worsening is detected.

The influencing factors and prevention progress of motor complications of Parkinson's disease / 预防医学

Abstract@#Long-term use of levodopa in the treatment of Parkinson's disease can cause motor complications, which seriously impair the patients'motor function, reduce the quality of life, and aggravate the functional disability. Since there has been no effective treatment for motor complications, clarifying the influencing factors and prevention methods are conducive to reducing the risk of incidence and improving the quality of life of the patients. This paper summarizes the types and mechanism of motor complications of Parkinson's disease, the influencing factors ( levodopa dose, onset age, Helicobacter pylori infection and high protein diet ) and preventive measures ( psychological intervention, low protein diet, rehabilitation exercise and drugs ), so as to provide reference for the prevention and control of the disease.

Blood pressure and its association with antiparkinsonian medications in patients with Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is the second most common neurodegenerative disease following Alzheimer′s disease. The non-motor symptoms of PD have attracted increasing attention. The occurrence of abnormal blood pressure is related to many factors, including aging, PD related autonomic nerve dysfunction, and drugs for PD treatment,including levodopa, dopamine receptor agonists. Abnormal blood pressure severely limits the clinical use of anti-PD drugs. In order to better understand the relationship between anti-PD drugs and blood pressure in patients with PD. This article summarizes the manifestations of abnormal blood pressure, and analyzes the correlation between anti-PD drugs and blood pressure, summarizes the possible mechanisms of how anti-PD drugs affects the blood pressure in PD.

Recent advance in treatment of dyskinesia in Parkinson's disease / 中华神经医学杂志

Parkinson's disease (PD) is a kind of common degenerative diseases of the nervous system. Levodopa replacement therapy is the most important clinical treatment method. However, long-term use can lead to the occurrence of dyskinesia and seriously affect the quality of life of patients. The current treatment methods for PD dyskinesia include drug therapy and non-drug therapy; most patients with dyskinesia can got improvement well by adjusting the dosage of drugs, changing the methods of administration, combination medication, or surgical treatments. Based on this, this article reviews the latest research on the treatment of PD dyskinesia to further help clinical colleagues effectively treat PD dyskinesia.

Distonia Responsiva à Levodopa: Síndrome de Segawa ­ Relato de Caso / Dopa-Responsive Dystonia: Segawa disease - Case Report

Iniciada geralmente na infância e adolescência, a doença de Segawa é um tipo de distonia progressiva responsiva à Levodopa causada por uma mutação genética no braço longo do cromossomo 14. Os sintomas pioram ao longo do dia e com o envelhecer, entretanto tornam-se estáveis por volta da quarta década de vida. Descrita em 1971, é uma doença rara e frequentemente subdiagnosticada ou diagnosticada erroneamente. O objetivo deste estudo é descrever a síndrome cuja distonia é o principal sintoma e trazer atenção para o tratamento, que geralmente evidencia-se boa resposta a Levodopa. No presente relato de caso há a história de uma paciente encaminhada a um ambulatório de neurologia, de 20 anos e do sexo feminino, com distonia de membros inferiores e tremor de membros superiores, com piora progressiva dos sintomas desde os 6 anos de idade. O tratamento foi iniciado, havendo boa resposta, porém com necessidade de aumento da dose ao longo dos anos devido à progressão dos sintomas. Portanto, apesar de ser de origem no sistema nervoso central, a remissão dos sintomas é mantida com o tratamento preconizado, trazendo excelente qualidade de vida ao paciente.

With symptoms starting in childhood and teenage years, the Segawa disease is a type of progressive dystonia responsive to levodopa, caused by a genetic change located on the long arm of chromosome 14. The symptoms worsen as the day goes by and as the patient gets older, becoming stable around the fourth decade of life. Initially described in 1971, it is a rare condition and under-diagnosis or misdiagnosis are frequent. The objetive of this study is to describe the syndrome in which dystonia is the main symptom and highlight its treatment, generally showing positive response to levodopa. In the present report, the patient referred to a neurology ambulatory was 20 years old, female, with lower limbs dystonia, as well as tremor affecting upper limbs, and manifestations worsening from 6 years of age. Treatment was started, with good response, even though higher dosages in the subsequent years were necessary due to the progression of symptoms. Thus, besides being originated in the central nervous system, the remission of symptoms is kept with the proposed treatment with excellent quality of life.

Diagnostic prediction model for levodopa-induced dyskinesia in Parkinson's disease / Modelo de predição diagnóstica para discinesias induzidas por levodopa na doença de Parkinson

Abstract Background: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. Objective: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. Methods: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. Results: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). Conclusion: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.

Resumo Introdução: No momento, não há métodos para se predizer o desenvolvimento de discinesias induzidas por levodopa (DIL), uma frequente complicação do tratamento da doença de Parkinson (DP). Preditores clínicos e polimorfismos de nucleotídeo único (SNP) têm sido associados às DIL na DP. Objetivo: Investigar a associação entre variáveis clínicas e genéticas com as DIL e desenvolver um modelo de predição diagnóstica de DIL na DP. Métodos: Foram avaliados 430 pacientes com DP em uso de levodopa. A presença de DIL foi definida como escore ≥1 no item 4.1 da MDS-UPDRS Parte IV. Nós testamos a associação entre variáveis clínicas específicas e sete SNPs com o desenvolvimento de DIL, usando modelos de regressão logística. Resultados: Em relação às variáveis clínicas, idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos estiveram associados às DIL. Apenas o genótipo CC do SNP rs2298383 no gene ADORA2A esteve associado com DIL após o ajuste. Nós desenvolvemos dois modelos preditivos diagnósticos com acurácia razoável, mas sugerimos o uso do modelo preditivo clínico. Esse modelo de predição tem uma área sob a curva de 0,817 (intervalo de confiança de 95% [IC95%] 0,77‒0,85) e sem perda significativa de ajuste (teste de qualidade de ajuste de Hosmer-Lemeshow p=0,61). Conclusão: A probabilidade prevista de DIL pode ser estimada, com acurácia razoável, por meio do uso de um modelo preditivo diagnóstico clínico, que combina a idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos.

Research progress of 6-18F fluoro-L-dopa PET/CT imaging / 中华核医学与分子影像杂志

6-[18F]fluoro-L-dopa (18F-DOPA) is a levodopa analogue.18F-DOPA PET/CT imaging is considered as an ideal tool in the diagnosis and evaluation of Parkinson's disease,brain tumors,pheochromocytoma/paraganglioma,neuroblastoma,gastrointestinal carcinoid,medullary thyroid cancer and congenital hyperinsulinemia.This paper reviews the synthesis,mechanism of localization,imaging procedures,clinical indications and research advances of 18F-DOPA.