Objective: The aim of this study was to determine the clinical, neurophysiological and biological features of Parkinson’s Disease (PD) patients with L-Dopa-induced dyskinesias (LIDs).

Background: The most effective treatment for PD is L-Dopa, however, as PD progresses, involuntary movements named LIDs, appear. Most of PD patients develop LIDs during the course of the disease and some of them after just after a few years of L-Dopa treatment.

Method: We collected clinical data of 104 patients. All patients underwent venipuncture for serum collection; 54 patients also underwent lumbar puncture for CSF collection. Total-alpha-synuclein (t-a-syn) levels were measured in both serum and CSF, with commercially available ELISA kits. Uptake values of 123I-FP-CIT-SPECT were available for 50 patients. A subgroup of 30 patients, 15 without LIDs and 15 with LIDs, underwent neurophysiological examination with TMS.

Results: Overall, patients had a mild parkinsonism (MDS-UPDRS III score 22 ± 13) with a mean disease duration of 8 ± 5 years and oral LEDD intake of 577 ± 422mg. LIDs were observed in 42 patients (Dysk), while 62 patients were defined as non-dyskinetic (Non Dysk). Patients with LIDs had a longer disease duration, higher LEDD intake and worse MDS-UPDRS III scores. Patients with LIDs showed a higher degree of putaminal dopaminergic denervation at diagnosis, measured with semiquantitative analysis of 123I. No differences were found in t-α-syn levels in patients with and without LIDs in both serum and CSF.

At the neurophysiological examination with TMS, a significant depotentiation in the group of Non Dysk patients and a not significant depotentiation in the group of Dysk patients was found. Furthermore, we found a significant negative correlation between the amplitude of depotentiation and the score of UDysRS part III in Dysk patients (r = -0.67, p = 0.006), i.e., the less depotentiation the more severe the LIDs.

Conclusion: From our data emerges that nigrostriatal DA denervation remains the major determinant in the pathogenesis of LIDs, while duration and dosage of L-Dopa treatment represent secondary factors, independently from other modifiable and non-modifiable risk factors. Conversely, t-a-syn levels in serum and CSF did not show any relationship with the presence of LIDs. Finally, the lack of homeostatic plasticity at both striatal and cortical regions is a constant pathophysiological feature of LIDs.

References: Eusebi P, Romoli M, Paoletti FP, Tambasco N, Calabresi P, Parnetti L. Risk factors of levodopa-induced dyskinesia in Parkinson’s disease: results from the PPMI cohort. NPJ Parkinsons Dis. 2018; 4:33. Published 2018 Nov 16. doi:10.1038/s41531-018-0069-x

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-neurophysiological-and-biological-insights-into-levodopa-induced-dyskinesias/