The Possible Role of Anti-Epileptic Drugs (AEDS) in Treating Levodopa Induced Dyskinesia (LID) | Biomedgrid llc

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease with a lifetime risk of 1–2%. It primarily affects the basal ganglia system (BG). Disruption of motor functions is one of the main clinical manifestations of PD. The main treatments of PD are L-dopa and dopamine receptor agonists. However, they are usually accompanied with dyskinesia (L-dopa induced dyskinesia or LID) which is common and very difficult to treat causing a significant decrease in patient’s quality of life. The exact mechanism beyond LID is largely unclear. A leading theory, based on the classical basal ganglia-cortical loop model, claimed that LID might be the result of dis-inhibition of the motor cortex (mainly the supplementary motor cortex or SMA) because of hypoactivity of GPi. At the cellular level, mechanisms involving pulsatile stimulation of dopamine receptors, dysregulation of genes and proteins in neurons resulting in changes in neural discharge patterns between BG and cortex were reported. Here, we are exploring the possible effects of anti-epileptic drugs (AED) in improving LID. AED are widely used agents mainly for controlling seizure disorders. Moreover, they have been used for other neurological and psychiatrial disorders. Part of the AED were investigated in PD patients with LID. Despite the lack of multiple wide prospective double-blind placebo-controlled trials, the current evidences provide possible positive effects in alleviating LID for at least part of AED such as Levetiracetam and others. We believe future clinical as well as pre-clinical research is recommended for properly investigating the effects of other AED in treating LID.

Body

Parkinson’s disease (PD) is a neurodegenerative disorder with a lifetime risk of 1%- 2% [1, 2]. Patients present with motor as well as non-motor symptoms and signs [1, 3, 4]. PD main motor signs are tremor, rigidity, bradykinesia, gait instability and more. Non-motor disturbances include sleep, autonomic problems and cognitive decline [1, 4]. PD is usually treated by drugs that enhance dopaminergic neurotransmission, such as levodopa and dopamine receptor agonists. These anti-parkinsonian drugs markedly improve motor performance, especially at the early stages of the disease. In contrast, in the more advanced stages of PD, patients only partially respond to the presently available pharmacological and neurosurgical treatments and develop severe adverse events to anti-Parkinsonian drugs [1, 5, [6, 7, 56]. One important complication of levodopa and dopamine receptor agonists is the levodopainduced dyskinesia (LID). LID develops in almost all long-standing PD patients treated with levodopa or dopamine receptor agonists, and manifests as involuntary movements induced by the anti- Parkinsonian drugs [8, 9].

Conclusion

To conclude, LID is a common and a difficult to treat complication in PD patients receiving L-dopa or dopamine agonists. Only part of AEDs were directly addressed to improve this dyskinesia. Levetritacem is the drug with the most evidences for treating LID with positive effects in most of the clinical studies. Others were not properly investigated with only small trials lacking statistical power and consistency in findings. Counting on the pathophysiological mechanism, AEDs and especially the voltagegated sodium channels blockers may help alleviate LID by reversing the dis-inhibited motor cortex and the irregular firing patterns of neurons in the motor cortex as well as striatum. Such drugs include phenytoin, Lacosamide, carbamazepine and Lamotrigine. Therefore, we recommend that larger trials will be conducted exploring the real effects of those drugs in LID patients.

Acknowledgements

Not to mention.

Conflict of Interest

No conflict of interest.

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The purpose of the American Journal of Biomedical Science and Research is to publish scientific and technical research papers, to bring attention to the importa