Rest tremor is one of the cardinal signs of
Parkinson's disease. Kinetic and postural
tremors may also occur. The coexistence of these three types of
tremor at disease onset and their subsequent progression could have important clinical and therapeutic implications but remain to be fully elucidated. We aimed to: (i) evaluate prevalence and progression of these three types of
tremor in early stages of the disease; and (ii) investigate longitudinally the relationship between dopaminergic and serotonergic terminal dysfunction,
rest tremor severity and its response to dopaminergic
therapy. The Parkinson's Progressive Markers Initiative database provided the baseline and 2-year follow-up clinical ratings and 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodophenyltropane (123I-FP-CIT) single photon emission computed tomography images for this study.
123I-FP-CIT measured putamen
dopamine transporter and median raphe
serotonin transporter availability. A raphe/putamen uptake ratio was calculated for each patient as an index of relative involvement of these structures. Clinical analysis of
tremor was conducted on 378 patients: 87.8% presented with
tremor at baseline;
rest tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up. Postural and kinetic
tremors occurred in about 50% of patients at both baseline and follow-up. Over 20% of patients presenting with
tremor did not exhibit a rest component at baseline. The number of patients with isolated
rest tremor was halved at follow-up. In
tremor predominant patients,
rest tremor severity was inversely correlated with raphe
serotonin transporter availability both at baseline and follow-up (baseline: constancy P < 0.05,
tremor index P < 0.05; follow-up: amplitude P < 0.05, constancy P < 0.05,
tremor index P < 0.05). In the entire cohort, more severe
tremor scores correlated with lower raphe/putamen uptake ratio values, indicative of more severe raphe dysfunction (baseline: constancy P < 0.01,
tremor index P < 0.05; follow-up: amplitude P < 0.01, constancy P < 0.001,
tremor index P < 0.001). The percentage of improvement in
rest tremor amplitude after acute dopaminergic
therapy was smaller in patients with lower raphe/putamen uptake ratio values (P < 0.01).
Rest tremor is the most represented type of
tremor in early
Parkinson's disease. However, postural and kinetic
tremor can affect approximately half of these patients and can occur in absence of
resting tremor. As disease progresses, both raphe serotonergic dysfunction and putamen
dopamine depletion could contribute to the occurrence of
rest tremor. The former is linked to more severe
tremor scores and poorer response to dopaminergic
therapy. Non-dopaminergic treatments might be beneficial for patients whose
tremor is associated with a raphe-predominant dysfunction.