Objective To investigate the clinical features of dyskinesia and related risk factors in female patients with Parkinson disease （PD）. Methods A cross-sectional study was conducted among the female patients who met the diagnostic criteria for PD at the outpatient service of PD in Aerospace Center Hospital， and demographic data and clinical data were collected and compared between groups， including levodopa equivalent daily dose （LEDD）， Unified Parkinson’s Disease Rating Scale-Ⅲ（UPDRS-Ⅲ）， UPDRS-Ⅳ， scores of non-motor symptoms （cognition and depression）， presence or absence of dyskinesia， and single levodopa dose （LD） during the onset of dyskinesia. A binary logistic regression analysis was used to investigate the influencing factors for dyskinesia in female patients with PD. Results A total of 146 female PD patients were enrolled， among whom 30 patients had dyskinesia， with an incidence rate of 20.5%. Compared with the non-dyskinesia group in terms of clinical features， the dyskinesia group had a significantly younger age of onset [（54.3±12.5） years vs （62.7±10.0） years， P<0.001]， a significantly longer disease duration [（9.9±3.7） years vs （4.5±3.7） years， P<0.001]， a significantly higher severity of disease [H-Y stage： （2.65±0.58） vs （2.35±0.83）， P=0.03]， a significantly longer duration of LD administration [（7.5±3.2） years vs （3.2±2.6） years， P<0.001]， a significantly higher LEDD [（703.2±203.9） mg vs （442.1±226.3） mg， P<0.001]， and significantly lower body weight [（54.1±8.2） kg vs （60.0±8.7） kg， P=0.001] and BMI [（20.9±3.1） kg/m2 vs （23.4±3.1） kg/m2， P<0.001]. The multivariate logistic regression analysis showed that high BMI （OR=0.770， P=0.005） was a protective factor against dyskinesia in female PD patients， while long disease duration （OR=1.304， P=0.001） and high LEDD （OR=1.003， P=0.012） were risk factors for dyskinesia. Conclusion There is a relatively high incidence rate of dyskinesia in female PD patients， which should be taken seriously in clinical practice， and high BMI is a protective factor， while long disease duration and high LEDD are risk factors for dyskinesia in female PD patients.
Parkinson Disease ; Dyskinesias ; Levodopa

Patients with Parkinson disease （PD） can have hand and foot deformities called “striatal deformities”， which often occur in the middle and late stages of PD， but also in the early stage. The clinical manifestations of such deformity are similar to those of hand-foot deformity due to osteoarticular diseases， and some patients may have pain and discomfort； however， the low incidence rate and few reports of this disease may easily lead to misdiagnosis and mistreatment.
Parkinson Disease ; Levodopa

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.
Female ; Humans ; Infant ; Male ; Benserazide/therapeutic use* ; Dystonia/genetics* ; Hypokinesia/drug therapy* ; Levodopa/pharmacology* ; Muscle Hypotonia ; Retrospective Studies ; Tyrosine 3-Monooxygenase/genetics*

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.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use. Six databases were searched to screen out the randomized controlled trial on the TCM compounds combined with levodopa medicine in the treatment of PD. Literature quality of the included studies was evaluated by improved Jadad rating scale, and the Meta-analysis was performed by RevMan 5.3 software. After the data of the basic TCM compounds involved were sorted out, the strong association rules were found by using Apriori algorithm of SPSS Modeler 18.0 software, and then the basic herbs for the treatment of PD could be picked out. A total of 20 studies were eventually included, involving 1 784 patients. Ten studies were of high-quality literature, Jadad score≥4 points. Meta-analysis showed that efficacy of TCM combined with levodopa medicine was better than levodopa medicine alone in lowering Unified Parkinson's Disease Rating Scale(UPDRS) score: UPDRS Ⅰ(MD=-0.43, 95%CI[-0.62,-0.24], P<0.000 1), UPDRS Ⅱ(MD=-2.72, 95%CI[-3.24,-2.21], P<0.000 01), UPDRS Ⅲ(MD =-1.97, 95%CI[-2.69,-1.25], P<0.000 01), UPDRS Ⅳ(MD=-0.28, 95%CI[-0.46,-0.11], P=0.002). And the improvement in UPDRS score reduction rate of TCM combined with levodopa medicine was better than that in levodopa medicine alone: effective rate(OR=4.81, 95%CI[3.50, 6.62], P<0.000 01). Data mining results showed that the basic prescription for treating PD consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Gastrodiae Rhizoma in general. According to each part of UPDRS, the basic prescription for treating mentation, behavior and mood(UPDRS Ⅰ) consists of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Among which Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle might have unique efficacy. The basic prescriptions for treating UPDRS Ⅱ and UPDRS Ⅲ consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata, or Chuanxiong Rhizoma-Angelicae Sinensis Radix(two drug combinations). However, in the treatment of UPDRS Ⅳ, the drugs were scattered. But due to the limitations in the quantity and quality of clinical studies, the results obtained still need further research and clinical confirmation of its efficacy.
China ; Drugs, Chinese Herbal ; Humans ; Levodopa ; Medicine ; Medicine, Chinese Traditional ; Parkinson Disease

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.
Cohort Studies ; Dyskinesias ; Humans ; Incidence ; Levodopa ; Methods ; Movement Disorders ; Parkinson Disease ; Retrospective Studies ; Washington

Parkinson's disease is one of the most common neurodegenerative disorders world widely. Although curable therapies are practically not available yet, symptomatic managements using anti-Parkinson medications have shown to be quite effective to improve patients' quality of life. The discovery of dopaminergic deficits in Parkinson's disease in 1960s have brought about the human clinical trials of levodopa, which opened an “Era of Dopamine” in treatment history of the Parkinson's disease. Levodopa still remains gold standard. Dopamine agonists have proved their efficacies and delayed the development of long-term complications of levodopa use. Inhibitors of respective enzyme monoamine oxidase-B and catechol-O-methyltransferase, anticholinergics, and amantadine strengthen the therapeutic effects via either monotherapy or adjunctive way. Strategy of continuous dopaminergic stimulation and disease modification are weighing in current advances. This article is providing evidence-based review of pharmacological treatment of Parkinson's disease from early to advanced stages as well as management its unavoidable adverse reactions.
Amantadine ; Catechol O-Methyltransferase ; Cholinergic Antagonists ; Dopamine Agonists ; Drug Therapy ; Humans ; Levodopa ; Neurodegenerative Diseases ; Parkinson Disease ; Quality of Life ; Therapeutic Uses

This study investigated the effects of ombuoside, a flavonol glycoside, on dopamine biosynthesis in PC12 cells. Ombuoside at concentrations of 1, 5, and 10 µM increased intracellular dopamine levels at 1 – 24 h. Ombuoside (1, 5, and 10 µM) also significantly increased the phosphorylation of tyrosine hydroxylase (TH) (Ser40) and cyclic AMP-response element binding protein (CREB) (Ser133) at 0.5 – 6 h. In addition, ombuoside (1, 5, and 10 µM) combined with L-DOPA (20, 100, and 200 µM) further increased intracellular dopamine levels for 24 h compared to L-DOPA alone. These results suggest that ombuoside regulates dopamine biosynthesis by modulating TH and CREB activation in PC12 cells.
Animals ; Carrier Proteins ; Dopamine ; Levodopa ; PC12 Cells ; Phosphorylation ; Tyrosine 3-Monooxygenase

OBJECTIVE: X-linked dystonia parkinsonism (XDP) is an adult-onset, progressive and debilitating movement disorder described among Filipino males from Panay Island. The available oral medications have been ineffective. While chemodenervation with botulinum toxin A works and deep brain stimulation surgery is promising, these are not affordable for the vast majority of patients. Thus, we decided to look into the efficacy, safety and tolerability of levodopa+carbidopa (levodopa) versus placebo among patients with XDP.

METHODS: This was a double blind, randomized, placebo-controlled clinical trial. Patients were randomized to receive levodopa or placebo for 6 months. The dose was increased gradually until 1000 mg levodopa/day is reached or until side effects appear.

RESULTS: A total of 86 out of 94 randomized patients (91.5%) were included in the intention-to-treat cohort for the primary efficacy analysis. Nineteen patients (9 in levodopa, 10 in placebo) dropped out or were lost to follow up. There was no significant difference in the baseline and last visit Burke Fahn Marsden Dystonia Rating Scale and the part III of the Unified Parkinson's Disease Rating Scale scores between levodopa and placebo. The most common adverse events in the levodopa group were increased movements, pain and nausea/ vomiting.

CONCLUSION: While levodopa is safe and well-tolerated, it does not have any effect in alleviating the dystonia or parkinsonism in XDP.

Dopa-responsive dystonia (DRD) is characterized by lower limb-onset, diurnally fluctuating dystonia and dramatic and sustained response to levodopa treatment. Segawa disease, an autosomal dominant deficiency of guanosine triphosphate cyclohydrolase 1 (encoded by GCH1) is the most common and well-known condition manifesting as DRD. However, similar clinical manifestations can be seen in individuals with deficiencies of other enzymes that are involved in the biosynthesis of dopamine. We describe the case of an 11-year-old girl who presented with abnormal gait, which had initially begun 2 years back. The patient showed diurnally fluctuating dystonia in both legs. She was able to walk without support in the morning, but was unable to stand without support in the evening. She had been diagnosed as having spastic cerebral palsy and had been managed with physical therapy at a local rehabilitation clinic. The patient had been healthy until the development of dystonia, and did not have a history of perinatal problems or developmental delay. Routine hematologic and biochemical test results were normal. Brain magnetic resonance imaging and electroencephalography showed no abnormalities. When levodopa was administered, the patient's abnormal gait dramatically improved 1 hour after receiving the medication. Genetic testing for the GCH1 gene revealed a missense mutation (c.293C>T [p.A98V]) that has previously been reported in patients with DRD. This case demonstrated that a levodopa trial is vital for accurate and early diagnosis of DRD in patients with dystonia resulting from an unknown cause.
Brain ; Cerebral Palsy* ; Child ; Diagnostic Errors ; Dopamine ; Dystonia* ; Early Diagnosis ; Electroencephalography ; Female ; Gait ; Genetic Testing ; Guanosine Triphosphate ; Humans ; Leg ; Levodopa ; Magnetic Resonance Imaging ; Mutation, Missense ; Rehabilitation