Less Pulsatile Levodopa Therapy (6 Doses Daily) Is Associated with a Reduced Incidence of Dyskinesia

Mark Muquan Lin,Robert Laureno 대한파킨슨병및이상운동질환학회 2019 Journal Of Movement Disorders Vol.12 No.1

Objective To evaluate whether less pulsatile levodopa therapy (LPT) can reduce the development of levodopa-induced dyskinesia (LID). Methods This is a retrospective cohort study of patients with Parkinson’s disease at the movement disorders clinic of Medstar Washington Hospital Center. The study was not blinded or randomized. Patients were seen between August 2002 and August 2018. During these years, we treated patients with less pulsatile (6 doses daily) levodopa treatment to reduce LID. Occurrence of LID was recorded. Results Ninety-five patients with Parkinson’s disease taking levodopa were divided into two groups: 1) patients who were initially managed on LPT or who switched from traditional therapy (TT) (n = 61) (mean disease duration: 7.7 ± 4.8 years, mean levodopa duration: 5.6 ± 4.5 years and mean observation time: 4.3 ± 3.4 years), and 2) patients on TT throughout the observation period or until they developed dyskinesia (n = 34) (mean disease duration: 8.3 ± 3.8 years, mean levodopa duration: 6.2 ± 4.2 years and mean observation time: 4.1 ± 3.4 years). Three of the 61 LPT patients developed dyskinesia during the observation period. One of the patients developed dyskinesia after being switched to pulsatile doses by another doctor. In the other two, dyskinesia was minimal. In contrast to this 4.9% cumulative incidence, dyskinesia occurred in 50% (17/34) of TT patients, an incidence similar to that in published data (p < 0.001). Conclusion Less pulsatile levodopa with 6 daily doses was associated with a low incidence of LID. Further study of this method of treatment is warranted.

Levodopa-induced respiratory dysfunction confirmed by levodopa challenge test : A case report

Ko, Pan-Woo,Kang, Kyunghun,Lee, Ho-Won,A., N/ Williams & Wilkins Co 2018 Medicine Vol.97 No.41

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P><B>Introduction:</B></P><P>Parkinson disease is associated with various nonmotor symptoms, including rare respiratory dysfunction events. However, patients with Parkinson disease often have comorbid medical problems, such as respiratory distress, and differentiating nonmotor symptoms can be difficult.</P><P><B>Case presentation:</B></P><P>A 78-year-old male presented with repetitive shortness of breath. He was diagnosed with Parkinson disease and chronic obstructive pulmonary disease (COPD) several years prior. His symptoms were ambiguous between acute COPD exacerbation and levodopa-related nonmotor symptoms of Parkinson disease. To clarify the underlying cause, we performed the levodopa challenge test. After the patient complained of dyspnea following levodopa administration, levodopa-induced respiratory dysfunction was diagnosed. After adjusting antiparkinson medication, the patient's respiratory symptoms gradually improved.</P><P><B>Conclusion:</B></P><P>Respiratory dysfunction as a nonmotor symptom of Parkinson disease can be caused by levodopa medication. To determine whether the symptoms are induced by levodopa, the levodopa challenge test may be useful in clarifying symptoms related to antiparkinson medication.</P></▼2>

Assessment of Bone Mineral Density of Patients with Spinocerebellar Ataxia Type 3

Aline Maria Santos Farias,Simone Appenzeller,Marcondes C França Jr.,Alberto RM Martinez,Elba E Etchebehere,Thiago F Souza,Allan O Santos 대한파킨슨병및이상운동질환학회 2019 Journal Of Movement Disorders Vol.12 No.1

Objective To evaluate whether less pulsatile levodopa therapy (LPT) can reduce the development of levodopa-induced dyskinesia (LID). Methods This is a retrospective cohort study of patients with Parkinson’s disease at the movement disorders clinic of Medstar Washington Hospital Center. The study was not blinded or randomized. Patients were seen between August 2002 and August 2018. During these years, we treated patients with less pulsatile (6 doses daily) levodopa treatment to reduce LID. Occurrence of LID was recorded. Results Ninety-five patients with Parkinson’s disease taking levodopa were divided into two groups: 1) patients who were initially managed on LPT or who switched from traditional therapy (TT) (n = 61) (mean disease duration: 7.7 ± 4.8 years, mean levodopa duration: 5.6 ± 4.5 years and mean observation time: 4.3 ± 3.4 years), and 2) patients on TT throughout the observation period or until they developed dyskinesia (n = 34) (mean disease duration: 8.3 ± 3.8 years, mean levodopa duration: 6.2 ± 4.2 years and mean observation time: 4.1 ± 3.4 years). Three of the 61 LPT patients developed dyskinesia during the observation period. One of the patients developed dyskinesia after being switched to pulsatile doses by another doctor. In the other two, dyskinesia was minimal. In contrast to this 4.9% cumulative incidence, dyskinesia occurred in 50% (17/34) of TT patients, an incidence similar to that in published data (p < 0.001). Conclusion Less pulsatile levodopa with 6 daily doses was associated with a low incidence of LID. Further study of this method of treatment is warranted.

레보도파제제의 위장관계 부작용에 대한 침치료 효과 연구 -특발성 파킨슨병 환자를 대상으로-

양동호,이경윤,신현승,조송현,임창선,임준혁,윤석훈,이한,강명진 대한침구의학회 2010 대한침구의학회지 Vol.27 No.6

Objective : This study was aimed at investigating the therapeutic effects of acupuncture on gastrointestinal side effect of Levodopa on idiopathic Pakinson’s disease patients. Methods : The subjects of this study were 42 patients with idiopathic Parkinson’s disease. We divided them into two groups; acupuncture treatment group, no treatment group. We treated the former group with acupuncture therapy focusing on gastrointestinal side effect of Levodopa while administering Levodopa as well. And the latter group was also dosed up with Levodopa without acupuncture therapy. To see the effect of acupuncture treatment clearly, we used gastrointestinal syndrome rating scale (GSRS) and visual analog scale (VAS) and compared the GSRS grade and VAS score of two groups statistically, after 1, 2, 3, 4 weeks since they have been under the treatment. Results : This study suggests that the group who has been treated with acupuncture on gastroin- testinal side effect of Levodopa on idiopathic pakinson’s disease patients showed higher GSRS grade and VAS score than the one that has not. But, We could’t find statistical significance between the two groups on improvement of GSRS grade and VAS score. Conclusions : These results proved that acupucture theraphy might be available for relieving symptoms related with gastrointestinal side effect of Levodopa than the one that has not. But further studies are necessary.

5-HT 수용체 길항제를 이용한 파킨슨 환자의 정신 증상의 치료

고성범,박건우,이대희,Koh, Seong-Beom,Park, Kun-Woo,Lee, Dae-Hie 대한생물정신의학회 1997 생물정신의학 Vol.4 No.1

Current treatment strategies for levodopa-induced psychosis in advanced Parkinson's disease have had limited success. Reduction or discontinuation of levodopa and coadministration with dopamine-blocking neuroleptics may attenuate the psychotic symptoms, but these strategies are associated with worsening of parkinsonian symptoms. Administration of 5-HT3 receptor antagonist ; ondansetron, a newer strategy to attenuate psychosis of Parkinson'disease without motor deterioration was introduced. A 41-year-old young-onset male, who was diagnosed as Parkinson's disease 7 years ago, was treated with levodopa therapy, and had levodopa-induced psychosis(delusion, hallucination, paranoid, insomnia). After trial of ondansetron, he showed improvement in the Brief Psychiatric Rating Scale(from 21 points to 9 points) in spite of increasing the dosage of levodopa. With ondansetron, we could increase the dosage of levodopa without psychotic complications(esp, hallucination), and he showed improvement in the motor fluctuation.

Continuous 24-h Levodopa-Carbidopa Intestinal Gel Infusion After a Levodopa Holiday Suppressed Refractory Dyskinesia Despite Increasing Levodopa Dose

Noriko Nishikawa 대한파킨슨병및이상운동질환학회 2022 Journal Of Movement Disorders Vol.15 No.3

Continuous delivery of levodopa–carbidopa intestinal gel (LCIG) to the jejunum can improve the symptoms of advanced levodopa-responsive Parkinson’s disease (PD) by allowing continuous dopamine stimulation. However, even after LCIG treatment initiation, it may be difficult to control levodopa-induced dyskinesia (LID), especially in females

Europium(3)와 EDTA의 3차 복합체 형성에 의한 Levodopa의 분광분석적 정량

( Mohammad Kamruzzaman ),( Md R-mahmnur Alam ),김소연 ( So Yeon Kim ),조해진 ( Hae Jin Jo ),이상학 ( Sang Hak Lee ),김영호 ( Young Ho Kim ),김성홍 ( Sung Hong Kim ) 한국공업화학회 2011 응용화학 Vol.15 No.1

A highly sensitive spectrofluorimetric method was developed for the determination of levodopa based on the formation of a ternary complex with Eu3+ in the presence of ethylenediaminetetraacetic acid. It was found that this complex manifests intense fluorescence at 591 and 613 nm with excitation at 372 nm and maximum intensity was obtained at 613nm. Under the optimum conditions, the enhanced fluorescence intensity was proportional to the concentration of levodopa over the range of 3×10(-9)-2.5×10(-7) mol L(-1) with limit of detection (LOD) of 4.37×10(-10) mol L(-1). The method offers higher sensitivity and selectivity which could be effectively applied for the determination of levodopa in pharmaceutical and biological samples.

Recent Advances in the Development of Experimental Therapeutics for Levodopa-Induced Dyskinesia

Michael L Martini,Sean N. Neifert,J Mocco,Fedor Panov,Winona Tse,Ruth H. Walker,Jian Jin,Fiona Gupta 대한파킨슨병및이상운동질환학회 2019 Journal Of Movement Disorders Vol.12 No.3

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, with an estimated prevalence of approximately 1% in people over 60, and it represents an increasingly important medical problem in our aging population [1]. For decades, the standard of care for PD has involved treatment with levodopa (L-DOPA), which elevates dopamine levels in the nigrostriatal pathway, enhancing movement and coordinated motor functions. Chronic L-DOPA results in motor complications, including levodopa-induced dyskinesia (LID), which occur in at least 50% of patients after 5 to 10 years of treatment. LID is a significant limitation to the viability of long-term L-DOPA use because patient function and quality of life are compromised and individual and societal costs are increased [2].

5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson’s Disease

Choi Yujin,Huh Eugene,Lee Seungmin,Kim Jin Hee,Park Myoung Gyu,Seo Seung-Yong,Kim Sun Yeou,Oh Myung Sook 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.4

Long-term administration of levodopa (L-DOPA) to patients with Parkinson’s disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

Association of metals with the risk and clinical characteristics of Parkinson's disease

Kim, Mi-Jung,Oh, Shin-Bi,Kim, Juyeon,Kim, Kiju,Ryu, Ho-Sung,Kim, Min Sun,Ayton, Scott,Bush, Ashley I.,Lee, Joo-Yong,Chung, Sun Ju Elsevier 2018 Parkinsonism & related disorders Vol.55 No.-

<P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>While metals have been implicated in the pathophysiology of Parkinson's disease (PD), the clinical evidence is scarce. Further, the contribution of metals for the risk or clinical presentation of PD remains to be explored.</P> <P><B>Methods</B></P> <P>To investigate the associations between the level of metals in blood serum and PD risk or clinical presentation, including sex-related differences, we studied 325 PD patients and age- and sex-matched 304 controls. We collected clinical data of the PD patients, including age at onset, PD duration, levodopa-equivalent dose (LED), Hoehn and Yahr stage (H-Y stage), presence of motor fluctuation, levodopa-induced dyskinesia (LID), freezing of gait, hallucination, and Mini-Mental State Examination (MMSE) score. Iron, copper, and zinc levels in serum were assayed by inductively coupled plasma mass spectrometry. Statistical analyses were performed to determine the sex-related differences in metal levels.</P> <P><B>Results</B></P> <P>Among the three metal elements tested, serum copper levels showed significant correlations with PD risk or clinical presentation. Higher copper levels were associated with a decreased PD risk. Higher copper or lower iron levels were associated with the risk of LID in women. Serum copper levels were negatively correlated with MMSE scores in PD patients.</P> <P><B>Conclusions</B></P> <P>This clinical study suggests significant associations between serum metal levels and PD risk or essential clinical features, demonstrating the possible roles of metals in PD pathogenesis or symptom development.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Clinical evidence on the implication of metal in Parkinson's disease (PD) is rare. </LI> <LI> Higher copper level in serum is associated with a decreased PD risk. </LI> <LI> Higher copper or lower iron is associated with levodopa-induced dyskinesia in women. </LI> <LI> Serum copper level is negatively correlated with MMSE scores in PD patients. </LI> <LI> There are associations between serum metals and PD risk or clinical presentation. </LI> </UL> </P>