Levodopa-Induced-Dyskinesias Clinical Features, Incidence, Risk Factors, Management and Impact on Quality of Life

Abstract

Levodopa-induced dyskinesias (LID) belong to the most common dose-limiting adverse effects of levodopa therapy. "Peak-dose" LID occur with the maximum effect of medication, 'diphasic dyskinesias' have a "beginning-and end-of-dose" pattern, and the, "off-period dyskinesia" occur during off-periods, most frequently in the early mornings and are typically dystonic in nature. The majority of patients will have developed dyskinesias after 10 years of treatment, and about 40-50% after 5 years. Occurrence of LID appears to be related to dose and duration of treatment with levodopa and severity and duration of disease. In addition, patients with younger age of onset have been reported to have an earlier onset and higher rate of LID. The important aetiological role of non-physiological pulsatile stimulation of dopaminergic receptors is increasingly recognized and more continuous dopaminergic stimulation with the longer acting dopamine agonists has been shown to reduce and delay the onset of dyskinesias. LID may not have a significant effect on quality of life in patients with early disease or in very advanced disease stages. when often other problems arise, but in other patients they may be severely disabling. Treatment strategies to overcome LID include adjustment of timing, type and amount of dopaminergic medication, treatment with amantadine and, in treatment resistant cases, stereotactic surgery involving deep brain stimulation or lesioning procedures. A number of other pharmacological options are also being explored. Several methods for the assessment of LID are available to attempt accurate assessment of efficacy, although all of these have limitations, and further evidence on their utility if needed.

Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques

“…It’s worth mentioning that both age and PMI values are comparable between healthy controls and PD patients (NC vs PD: Age, P = 0.0672; PMI, P = 0.2494, Mann-Whitney U test; for further details, see Table 1), thus suggesting that such a downregulation is most likely associated to the pathological condition, rather than demographic sample features. On the other hand, in line with previous findings [38], dyskinetic patients analysed here showed a longer accumulated lifetime L-DOPA ( P = 0.0408) and duration of L-DOPA treatment ( P = 0.0391), compared to non-dyskinetic subjects (Table 1). …”

Zooming in on the small: The plasticity of striatal dendritic spines in l‐DOPA–Induced dyskinesia

“…Furthermore, the studies did not state whether any of the patients had suffered from L-DOPA-induced dyskinesia, which is very common in PD patients with disease (and treatment) duration longer than 5 to 6 years. 37 FIG. 2.…”

Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study

“…Impulse control disorders (ICDs) and related behaviors and levodopa-induced dyskinesia (LID) are relatively frequent complications (17% and 80% respectively) in Parkinson's disease (PD). [1][2][3][4][5] The frequency of motor complications and dyskinesia increases with disease duration and long-term exposure to levodopa therapy. 1 By contrast, the relationship of ICDs and related behaviors with dopaminergic treatment duration and dose is less well established.…”