Objective: To longitudinally describe the course and clinical characteristics of tremor in Parkinson Disease (PD) over a seven-year follow up.

Background: Tremor is a cardinal symptom of PD and one of the most troublesome manifestations. Dopaminergic medications may have a suboptimal effect on tremor, compared to other cardinal symptoms.

Method: 423 patients recruited in the Parkinson Progressive Markers Initiative (PPMI) were considered. MDS-UPDRS III scores were used to evaluate tremor. After baseline, we evaluated yearly follow-ups for the first seven years. At each assessment we analyzed: the pattern and clinical severity of rest, postural, and kinetic tremors according to MDS-UPDRS III scores; the response of tremors to dopaminergic therapy.

Results: 96.9% of patients exhibited tremor during the first seven years. The most common tremor pattern was the combination of rest, postural and kinetic tremors (about 30% of the cohort at each assessment); rest tremor was the most frequent type of tremor in the cohort (65-70% of tremulous patients at each assessment). Mean scores of the three types of tremors tended to worsen and to spread from unilateral to bilateral (bilateral: 6.7% of the cohort at BL vs 31.5% at 7y). The proportion of patients with a MDS-UPDRS tremor score >2 in a single upper limb increased from 6% to 22%. Tremor response to dopaminergic therapy was documented at each assessment by a significant decrease in MDS-UPDRS tremor scores from the OFF to the ON state. The proportion of tremulous patients who showed a full response (75-100% improvement) to dopaminergic therapy increased over time, e.g. for rest tremor from 17.4% (1y) to 45.6% (7y). Conversely, the percentage of non-responders (improvement <25% or worsening) decreased over time for all types of tremor, e.g. from 49.3% of patients with rest tremor (1y) to 25.6% (7y).

Conclusion: Almost all patients experienced tremor over the 7-year follow up. The proportion of patients with tremor decreases over time, but tremors tend to spread bilaterally and to show increasing scores. A reduction in mean tremor scores from OFF to ON is always evident at the cohort level. However, a non-negligible proportion of patients is non-responsive. A complete response of rest tremor is shown in less than 50% of patients at all time points. These data show that along dopaminergic agents, other medications are needed to tackle tremor in PD.

References: [1] Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020;323(6):548–560. doi:10.1001/jama.2019.22360 [2] Fishman, P.S. (2008), Paradoxical aspects of parkinsonian tremor. Mov. Disord., 23: 168-173. https://doi.org/10.1002/mds.21736 [3] Marek, K., Jennings, D., Lasch, D., Siderowf, A., Tanner, C., et al. The Parkinson Progression Marker Initiative (PPMI), (2011) Progress in Neurobiology, 95: 629-635. https://doi.org/10.1016/j.pneurobio.2011.09.005. [4] Goetz, C.G., Tilley, B.C., Shaftman, S.R., Stebbins, G.T., Fahn, S., et al. (2008), Movement Disorder Society‐sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS‐UPDRS): Scale presentation and clinimetric testing results. Mov. Disord., 23: 2129-2170. https://doi.org/10.1002/mds.22340

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-course-of-tremor-in-de-novo-pd-7-year-longitudinal-analysis/