A new quantitative rating scale for dyskinesia in nonhuman primates

Abstract

The aim of this study was to develop a quantitative scale to assess levodopa-induced dyskinesias (LID) in non-human primates using a video-based scoring system (Quantitative Dyskinesia Scale, QDS). Six macaques with stable parkinsonism and LID were used for tests of the new QDS, in comparison with our current standardized scale (Drug Related Side-effects, DRS), which provides a classic subjective measurement of dyskinesia. QDS scoring is based on systematic movement counts in time frames, using videotape recordings. For both scales, body segments scored included each extremity, trunk, neck and face, and raters were blinded to L-dopa treatments. Comparisons of the two scales revealed that their scores are highly correlated and parallel to the L-dopa pharmacokinetic profile, although the QDS provided significantly more quantifiable measurements. This remained the case after separating animals into groups of mild and severe dyskinesias. Inter-rater reliability for application of the QDS was confirmed with scores obtained by three examiners. We conclude that the QDS is a quantitative tool for reliably scoring LID in parkinsonian monkeys at all levels of severity of dyskinesia. The application of this new standard for scoring LID in primates will allow for more precise measurements of the effects of experimental treatments and improve the quality of results obtained in translational studies.

A Selective Phosphodiesterase 10A Inhibitor Reduces L‐Dopa‐Induced Dyskinesias in Parkinsonian Monkeys

“…Motor evaluations were performed using a standardized primate motor scale (PMS) for MPTP‐treated monkeys (see the scale in Supplementary Information) . The PMS has two parts: motor disability is rated in Part I (which is similar to Part III of the UPDRS used for PD patients), and LIDs are rated in Part II .…”

“…Motor evaluations were performed using a standardized primate motor scale (PMS) for MPTP-treated monkeys (see the scale in Supplementary Information). [30][31][32] The PMS has two parts: motor disability is rated in Part I (which is similar to Part III of the UPDRS used for PD patients), and LIDs are rated in Part II. 28 In addition, animals were assessed with the Drug Effects on the Nervous System (DENS) scale 33 to evaluate other potential neurological side effects of MR1916 or amantadine.…”

Rating scale for parkinsonian motor signs in macaques and other non‐human primates v1

“…There are a variety of such scales available, each differing slightly by areas of emphasis. [1][2][3]…”

Striatal neurons in the development of levodopa-induced dyskinesias in Parkinson’s disease

“…For example, a couple groups have used motion sensor and accelerometers to track dyskinesia and severity in PD patients with LIDs and found that they could separate LID activity reliably from PD symptoms (Keijsers et al, 2003;Mera et al, 2012). Similar studies in non-human primates are also promising (Potts et al, 2015). Though still preliminary, studies such as these are promising and could lead to significant advances in the way physicians look at LIDs and provide insight into the mechanism of movement disorders.…”

“…Recently, a group studied the use of a quantitative video-based scoring method in the MTPT primate model to more objectively study LIDs (Potts et al, 2015). Studies such as this highlight how technological advances may aid in the clinic as not all patients will present with the same LID severity and expression of LID subtypes.…”