Table 1
Subject demographics and compliance summary. Abbreviations: Avg, average; SD, standard deviation; BL, bilateral; L, left; R, right.
| Age (yrs) | Disease duration (yrs) | Tremor frequency (Hz) | Medications | Stimulated hand | Enrollment days | Completed TAPS sessions | Compliance# (%) | |
|---|---|---|---|---|---|---|---|---|
| 1 | 75 | 25 | BL: 5.3–5.4 | Propranolol and primidone | Right | 86 | 156 | 90.70 |
| 2 | 62 | 30–40 | BL: 4.5–5.0 | Propranolol | Right | 88 | 131 | 74.43 |
| 3 | 74 | 57 | L: 3.8–4.2 R: 4.0 | Propranolol, primidone, gabapentin, and acetazolamide | Left | 97 | 67 | 34.54 |
| 4 | 71 | 30–35 | BL: 5.2–5.8 | Primidone and gabapentin | Right | 85 | 171 | 100.00 |
| 5 | 69 | 10–12 | BL: 4.9–5.3 | None | Right | 90 | 156 | 86.67 |
| Avg | 70.2 | 89.2 | 136.2 | 77.3 | ||||
| SD | 5.2 | 4.8 | 41.3 | 25.6 |
[i] # % Compliance is based on twice a day use during enrollment days = (100 * No. of completed TAPS sessions)/(2 * No. of enrollment days).
Figure 1
PET results and PET-tremor correlation: (A–G) PET imaging of TAPS-induced brain regional activity at day 90, compared to day 1, averaged across 5 subjects with essential tremor (p<0.05, uncorrected), showing (A, C) hypermetabolic clusters in ipsilateral cerebellar hemisphere and (E) a hypometabolic cluster in contralateral cerebellar hemisphere. (B, D, F, G) Cerebellar connectivity atlas showing cerebral-cortical connections for different cerebellar regions- the red color for example shows connection to frontal pole and medial frontal cortex and the orange color shows connection to frontal and parietal cortex, including premotor region. (H) Pre-TAPS clinical tremor scores (TETRAS) on day 1 and day 90 for all 5 ET patients. (I) Absolute change of SUVR for the three cerebellar clusters shown in (A),(C) and (E) at day 90 compared to day 1. (J) Correlation between change of tremor scores and SUVR for the cerebellar clusters from day 1 to 90. Abbreviations: CL, contralateral; ET, essential tremor; IL, ipsilateral; PET, positron emission tomography; TAPS, transcutaneous afferent patterned stimulation; TETRAS, Tremor Research Group Essential Tremor Rating Assessment Scale; SUVR, standardized uptake value ratio. p-values: * <0.05, ** <0.01, *** <0.0005.
Table 2
PET results: Regions showing statistically significant changes in 18F-fluorodeoxyglucose (FDG) uptake at day 90 compared to day 1 following longitudinal TAPS therapy (p<0.05, uncorrected). Abbreviations: CL, contralateral; IL, ipsilateral.
| Region | Maximum T-score | Cluster size | Talairach coordinates | ||
|---|---|---|---|---|---|
| x | y | z | |||
| IL Cerebellum crus II cluster 1 | 3.45 | 145 | 34.5 | –70.5 | –39 |
| IL Cerebellum crus II cluster 2 | 3.29 | 61 | 39 | –54 | –45 |
| IL Precentral area | –2.65 | 40 | 15 | –21 | 52.5 |
| IL Postcentral area | –3.05 | 85 | 60 | –13.5 | 10.5 |
| IL Middle occipital | –3.29 | 54 | 24 | –81 | 1.5 |
| CL Cerebellum Lobule IX | –2.73 | 40 | –13.5 | –42 | –33 |
| CL Insula | –2.77 | 98 | –34.5 | –12 | 10.5 |
| CL Cuneus | –3.1 | 47 | –7.5 | –79.5 | 10.5 |
| CL Anterior cingulate | –3.26 | 171 | –1.5 | 45 | 0 |
| CL Inferior parietal | –3.77 | 40 | –43.5 | –46.5 | 43.5 |
Figure 2
Tremor assessment: Clinician-rated change in TETRAS scores for both (A) stimulated and (B) non-stimulated hand at day 1 and day 90 (n = 5). (C) Tremor power before (black dot) and after (blue dot) each stimulation session (connected with a line) followed over a 90 days period for one of our representative subjects showing a decrease in tremor power after most stimulation sessions. Other subjects’ data is provided in the supplementary information (Figure S1). (D) Change in pre- and post-TAPS tremor power (pair-wise comparison) for individual subjects over the 90 days of use. The difference in Y-scales indicates inter-subject variability in tremor severity. Abbreviation: TAPS, transcutaneous afferent patterned stimulation; TETRAS, Tremor Research Group Essential Tremor Rating Assessment Scale. p-values: * <0.05, ** <0.01, **** <0.0001.