Resting tremor is the most common type of tremor found in early Parkinson disease (PD) and continues to be present at up to 2 years due to raphe serotonergic dysfunction and putamen dopamine depletion during PD progression, according to study findings published in Brain.
Investigators obtained 2-year follow-up clinical patient data as well as 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodo-phenyltropane (123I-FP-CIT) single photon emission computed tomography (SPECT) images from the Parkinson’s Progressive Markers Initiative database to assess for the prevalence and progression of resting tremor, postural tremor, and kinetic tremor during early PD. The 123I-FP-CIT SPECT imaging quantified median raphe serotonin transporter and putamen dopamine transporter availability. Using these data, researchers also sought the long-term association between serotonergic and dopaminergic terminal dysfunction, severity of resting tremor, and response to dopaminergic treatment.
A total of 378 patients, 87.8% (n=332) of whom had tremor at baseline, were included in the final analysis. At baseline and 2-year follow-up, 12.2% (n=46) and 16.1% (n=61) of patients had no evidence of tremor. In the entire cohort, 69.6% (n=263) of patients presented with resting tremor at baseline and 67.9% (n=257) of patients had resting tremor at 2-year follow-up.
Approximately 50% of patients presented with kinetic (46.8%, n=177) and postural (49.5%, n=187) tremors at baseline and follow-up. The presence of bilateral tremor was associated with higher amplitude in the most-affected limb (2.26±0.73 vs 1.79±0.68; P <.001), greater constancy (2.69±1.04 vs 2.09±1.05; P <.001), and higher index of resting tremor (6.44±3.59 vs 4.13±3.07; P <.001) compared with unilateral tremor.
At baseline and follow-up, the severity of resting tremor was found to be inversely correlated with raphe serotonin transporter availability in tremor-predominant patients (constancy P <.05, tremor index P <.05 [baseline] vs amplitude P <.05, constancy P <.05, tremor index P <.05 [follow-up]). Greater severity of tremor was associated with significantly higher raphe dysfunction severity (constancy P <.01, tremor index P <.05 [baseline] vs amplitude P <.01, constancy P <.001, tremor index P <.001 [follow-up]). In addition, acute dopaminergic therapy was associated with a smaller improvement in resting tremor amplitude in patients with lower raphe/putamen uptake (P <.01).
The reduction of the number of patients with tremor at follow-up may have been attributed to the residual effect of medications unaccounted for in the initial analysis. Also, the higher percentage of patients with a tremor-dominant phenotype included at baseline may have provided an overestimation of the number of tremors presented at both baseline and follow-up.
Utilizing 123I-FP-CIT SPECT imaging of raphe serotonergic nuclei and putamen dopaminergic terminals “could be important in the clinical setting in order to detect factors that might influence the response of tremor to dopaminergic medication.”
Pasquini J, Ceravolo R, Qamhawi Z, et al. Progression of tremor in early stages of Parkinson’s disease: a clinical and neuroimaging study [published online January 22, 2018]. Brain. doi:10.1093/brain/awx376