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Risk Factors for Levodopa-induced Dyskinesia in Parkinson’s Patients Study

Levodopa-induced Dyskiensia is a common complication of Parkinson's disease. Learn about the risk factors this study highlights.

Risk Factors for Levodopa-induced Dyskinesia in Parkinson’s Patients Study

There are motor as well as some non-motor symptoms that characterize Parkinson's' disease. PD causes rigidity, tremors, motor disabilities, and the possibility of fall, as well as non-motor symptoms, including anxiety and depression. The most effective treatment to control Parkinson’s systems to date is Levodopa. It has been found, however, that long-term use of Levodopa, which is a biologically active form of dopa, can lead to motor issues and other side effects. 

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Levodopa-induced dyskinesia (LID) refers to the movement disorders characterized by involuntary muscle movements and is a side effect commonly caused by the extended use of the medication Levodopa. Levodopa is the preferred medication used in treating Parkinson’s disease and other movement disorders, such as Huntington’s disease when rigidity is the main symptom.

There are seven risk factors for patients to develop Levodopa-induced dyskinesia. These include long-term treatment with Levodopa, being female, having Parkinson’s disease-associated mutations, having a higher severity of the disease at diagnosis, or having neuropsychiatric symptoms.

There are also side effects of Levodopa that make it a drug that needs to be monitored. If you read the fine print on the bottle of carbidopa-levodopa, it gives possible side effects of mood swings, depression, fear, and anxiety. Users state that these side effects are awful to experience, and the feelings of suicidal ideation are almost worse than the motor disabilities

The study is intended to find out if diagnosis in the early phase of Parkinson’s disease can improve management of the disease and help design the future of biomarker studies that predict who is at risk of Parkinson’s.

The Study

The study is based on finding the level of Levodopa dosages that cause LID.

Research published in the journal npj Parkinson’s Disease states that long-term dopamine repletion medication may lead to dyskinesia. Studies go on to say that over 50 percent of Parkinson’s patients who have used levodopa for over five years are at risk of developing Levodopa-Induced Dyskinesia (LID).

Risk factors for LID are the dosages and length of treatment, being underweight, and being female. The Parkinson’s Progression Markers Initiative, started in 2010 and is still ongoing. It's intended to observe the disease's progression in newly diagnosed Parkinson’s patients who are not yet being treated with Levodopa.

Biomarkers are analyzed and include the amount of the tau protein as well as its altered version. Tau proteins form tangles in the neurons in Parkinson’s patients and amyloid-beta, a protein found in Alzheimer’s disease.

A study by Odpedle S. Maria della Misericordia in Perugia, Italy was determined to define the factors that predicted LID development in de novo Parkinson’s patients.

In the study, data from 423 patients were studied. The follow-up was 4.6 years after the beginning of the study and the average time to start dopaminergic therapy was one year. Disease duration, anxiety, and high scores on the Movement Disorder Society-Unified Parkinson’s Disease rating scales par III predicted when dopaminergic treatment should be initiated.

About 109 of 390 patients analyzed had LID, and 33 of them lacked data regarding Levodopa treatment or LID onset. The study found that the average time to acquire LID was 3.6 years and the average onset time was 5.81 years from the initial Parkinson’s diagnosis. The time of 5.81 is an actual follow-up duration.

Risk factors for developing LID are being a woman, being classified as not as functionally independent as measured by the modified Schwab & England Activities of Daily Living scale (inability to take high care of yourself), high MDS-UPDRS part III score, postural instability, and gait disturbance. Also, high DaTscan caudate asymmetry index, which discusses the difference in the levels of dopamine transport between two different areas of the brain involved in motor control were studied. Additional risk factors include high genetic risk codes and anxiety. No cerebral or spinal fluid biomarkers predicted LID development. The onset of dyskinesia is also positively associated with depression and anxiety.

All these factors combined with the variable of 1,000 mg/day of Levodopa equivalent daily dose was found to be an accurate predictor of dyskinesia onset.

Researchers stated, “In summary, our findings indicate that data deriving from a large cohort of de novo PD patients monitored longitudinally are useful in understanding the composite aspects involved in the progression of disease.”

Motor fluctuation caused by Levodopa-induced Dyskinesia cause massive disruptions in the quality of life of people with Parkinson’s disease. The possibility of LID occurring in patients who use the drug long-term, has triggered a significant study to look for advanced treatments that can better manage Parkinson’s disease.

Results of the Study

Levodopa-induced dyskinesia negatively brings problems to the quality of life of patients with Parkinson’s disease. Extensive research has been conducted, but conflicting results have been found regarding the modifiable and non-modifiable risk factors for LID development. A set of several risk factors for LID development was identified and needs to be taken into consideration already in the early phases of the disease.

We know that female gender represents a non-modifiable predictive factor for LID and this is independent of genetic and body weight factors that can be changed.

Results also underline that continual usage of Levodopa is positively associated with the development of LID. It is important to note that Levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or a key pathophysiologic element in the development of dyskinesia or motor loss.

Dyskinesia in Parkinson’s disease comes with changes in long-term neuroadaptation and neuronal synaptic plasticity, which are linked to dopamine transports.

Using Positron emission tomography, PET, and single photon emission computed tomography, SPECT, changes in neurotransmitter pathways involved in motor loss or dyskinesia and was identified biomarkers for LID development.

Results show that dopamine effects in the contralateral putamen in de-nova Parkinson’s patients are a different predictor of time for levodopa to be initiated. Putamen asymmetry and caudate asymmetry evaluated by scientific projectors correlate with the development of dyskinesia. Findings reflect previous evidence that indicated there is a positive relationship between the asymmetric striatal index and the magnitude of response to levodopa. Patients with higher striatal asymmetric indexes have an increased response to levodopa and dyskinesia.

The final summary of the study indicates that data coming from a large cohort of de-novo Parkinson’s disease patients, who are monitored for a long time, are useful in understanding the elements involved in the progression of the disease. Results highlight the role of several factors in determining dyskinesia, and also provide useful information for future funding of clinical trials and biomarker studies.