Table 4.
Brief summary of study design with regard to different prodromal markers.
| Prodromal markers | References | Place | Study design | Number of subjects | Main results | |
|---|---|---|---|---|---|---|
| Follow-up ET patients (direct evidence) | SN hyperechogenicity | Sprenger et al. (27) | Austria | Prospective follow-up cohort study Follow-up: mean 6.16 ± 2.05 years | 70 ET patients | The relative risk for developing PD in patients with ET who had hyperechogenicity at baseline versus those without this hyperechogenicity was 7.00 (95 CI, 1.62–30.34; sensitivity, 77.8%; specificity, 75.6%) |
| Cardaioli et al. (28) | Italy | Longitudinal study Follow-up: 3-year | 79 with PD, 59 with ET and 50 matched controls | The maximum size of the SN hyperechogenicity was as follows: 5.62 ± 5.40 mm2 in the control group, 19.02 ± 14.27 mm2 in patients with PD, 9.15 ± 11.26 mm2 in patients with ET-, 20.05 ± 13.78 mm2 in patients with ET+ and 20.13 ± 13.51 mm2 in patients with ET-PD. ET-PD maximum values were significantly different from controls. Maximum values in patients with ET+ were different from both controls and patients with ET | ||
| Explore the characteristics of ET, PD, or ET-PD patients | SN hyperechogenicity | Budisic et al. (26) | Croatia | Case-control study | 80 PD patients, 30 ET patients, and 80 matched controls | Bilateral SN hyperechogenicity over the margin of 0.20 cm (2) was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET |
| Patients or make differential diagnosis (partial lateral evidence) | Circumscribed resting tremor | Minen and Louis (44) | USA | Retrospective study | 53 ET-PD, 53 PD and 150 ET patients | The initial cardinal sign of PD was rest tremor in 100% of patients. In ET-PD, the side of greatest initial ET severity usually matched that of greatest PD severity (P < 0.05) |
| Late onset asymmetrical postural tremor | Chaudhuri et al. (45) | UK | Longitudinal study | 13 ET-PD patients | After a variable and long latent period all patients developed additional signs suggesting a clinical diagnosis of PD although picking up an initial label of ET | |
| TSI | di Biase et al. (48) | Italy | Cohort study | 16 TDPD and 20 ET patients | TSI with a cut-off of 1.05 gave good classification performance for PD tremor and ET, in both test and validation datasets | |
| Olfactory decline | Louis et al. (50) | USA | Case-control study | 83 ET patients and 69 controls | In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho = −0.46, p < 0.001) | |
| Cognitive decline | Louis et al. (53) | USA | Clinical-epidemiological study | 30 ET-PD and 53 age-matched PD patients | The MMSE score was lower in ET-PD than PD [26.5 ± 3.1 (median 28.0) vs. 28.4 ± 2.2 (median 29.0), p = 0.001]. The TICS score was lower in ET-PD than PD [31.7 ± 3.9 (32.0) vs. 35.0 ± 2.0 (35.0), p < 0.001] | |
| Sleep disorder, especially RBD | Lacerte et al. (87) | Canada | Cross-sectional study | 50 ET patients | Using a screening questionnaire for RBD, 43.5% of ET patients are possibly suffering from RBD, whereas in the general population prevalence is estimated to be 0.5% | |
| HRV | Yoon et al. (94) | South Korea | Case-control study | 23 with ET, 27 with TDPD and 23 healthy controls | In the TDPD group, SDNN, LF, HF, and TP were significantly lower than those in the ET group. In a receiver operating characteristic AUC analysis, LF was the best potential diagnostic marker (AUC = 0.87) | |
| Others | Yavuz et al. (129) | Turkey | Case-control study | 15 ET, 7 ET with resting tremor, 25 ET-PD, 10 PD and 12 healthy subjects | Probability of ASR was significantly lower in ET-PD group whereas it was similar to healthy subjects in ET and PD (P < 0.001). LLR II was more common in ET, PD and ET-PD groups. LLR III was far more common in the PD group (n = 3, 13.6% in ET; n = 4, 16.0% in ET-PD and n = 7, 46.7% in PD; p = 0.037) |
ET, essential tremor; SN, Substantia nigra; PD, Parkinson's disease; ET-PD, new-onset of PD in patients previously diagnosed with ET; ET+, ET developed new-onset parkinsonian features, without fulfilling criteria for PD diagnosis; ET-, ET patients did not develop parkinsonian features; TSI, Tremor stability index; TDPD, tremor-dominant PD; UPSIT, the University of Pennsylvania Smell Identification Test; MMSE, Mini-Mental State Examination, TICS, Telephone Interview for Cognitive Status; RBD, REM sleep behavior disorder; HRV, Heart rate variability; SDMN, standard deviation of the normal-to-normal RR interval; LF, low-frequency; HF, high-frequency; TP, total spectral power; AUC, area under the curve; ASR, auditory startle reaction; LLR, long latency reflex.