Table 1
Summary of Neurophysiological Studies in ET, by Year of Publication
| Study | Methods Evaluated | TMS Measures Assessed | Findings |
|---|---|---|---|
| Britton et al.10 | Single pulse TMS M1 (suprathreshold) | Tremor phase, resetting index | Pulse to M1 resets ET tremor and PD tremor phase; latency to first peak significantly longer in PD tremor than ET tremor |
| Pascual-Leone9 | Single pulse TMS M1 (suprathreshold) | Tremor phase | Pulse to M1 resets tremor motor unit activity; resetting correlated with stimulus intensity and duration of post-stimulus silent period |
| Romeo et al.14 | Single pulse TMS M1 | Resting motor threshold, CSP, SICI | No difference in ET subjects compared to HC |
| Pinto et al.34 | Single pulse TMS cerebellum and paired pulse TMS: Cerebellar-M1 | MEP, CBI, tremor phase | Did reduce MEP at ISI 5–7 ms, but degree of inhibition not different in ET vs. HC (n = 9 vs. 10)No tremor reset with cerebellar TMS but there was w/ M1 TMS |
| Shukla et al.15 | Single pulse TMS M1, maximum stimulatory intensity | CSP | No statistically significant difference between ET subjects and HC; no correlation with disease duration |
| Molnar et al.13 | Single pulse TMS M1 with and without active DBS | MEPs, SICI, ICF, LICI | DBS facilitates MEPs especially at higher intensities; DBS has no effect on SICI or ICF, nor LICI ET subjects had reduced ICF at rest compared to HC but otherwise SICI, LICI and active ICF were no different from HC |
| Lo et al.11 | Motor imagery before and during single pulse TMS measures to M1 | RMT and MEPs | Motor imagery increase MEPs in HC but not ET; RMT were reduced during motor imagery in HC and ET |
| Mazzocchio et al.12 | Single pulse TMS to M1 in both adducted and abducted shoulder positions | MEPs | In subjects with ET, MEPs were facilitated in the abducted position, similar to HC, opposite of those with parkinsonian tremor |
| Avanzino et al.17 | Cerebellar rTMS using figure of 8 coil, handle up, right lateral cerebellum, 1 Hz at 90% RMT for 10 minutes | Touch duration and intertapping interval | At baseline, ET subjects have longer touch duration (TD) and shorter intertapping interval (ITI); 1 Hz TMS appear to restore TD and ITI to normal values |
| Chuang et al.16 | Premotor and motor cTBS | MEP, SICI, Tremor frequency and amplitude | cTBS reduces MEP in both HC and ET, but less durable in ET subjects; Reduces SICI No change in tremor frequency but significantly reduced tremor amplitude |
| Lu et al.33 | Single and paired pulse TMS (LICI paradigm) to M1, SMA and cerebellum | Tremor reset | M1 and SMA single pulse resets postural tremor in ET subjects Cerebellar single and paired pulse TMS did not reset postural tremor in ET |
| Brittain et al.50 | Cerebellar transcranial alternating current (tACS): active electrode (35 cm2): 3 cm lateral to inion | Frequency tolerance (stability of tremor over range of tremor frequencies) | ET has narrow frequency tolerance while PD tremor has broad frequency tolerance Cerebellar tACS is able to entrain ET tremor more than PD tremor |
| Hanajima et al.40 | Paired pulse cerebellar-M1 pulse using double cone 110-mm coil | CBI | CBI reduced in ET compared to HC |
[i] Abbreviations: CBI, Cerebello-brain Inhibition; cTBS, Continuous Theta Burst Stimulation; CSP, Cortical Silent Period; DBS, Deep Brain Stimulation; ICF, Intracortical Facilitation; ISI, Interstimulus Interval; LICI, Long Intracortical Inhibition; M1, Primary Motor Cortex; MEP, Motor Evoked Potential; RMT, Resting Motor Threshold; rTMS, Repetitive TMS; SICI, Short Intracortical Inhibition; SMA, Supplementary Motor Area; tACS, Transcranial Alternating Current Stimulation; TMS, Transcranial Magnetic Stimulation.
Table 2
Summary of Clinical Studies of Transcranial Stimulation in ET, by Year of Publication
| Study | Method of Stimulation | Target Location | Method of Assessment | Outcome |
|---|---|---|---|---|
| Gironell et al.41 (n = 10 ET) | Single session repetitive cerebellar TMS, 1 Hz, 70 mm butterfly coil, 100% maximal output, 30 trains of 10 seconds each | 2 cm caudal to inion | Tremor Rating Scale (TRS), accelerometry | Improved TRS and accelerometry ratings at 5 minutes but returned to baseline by 60 minutes |
| Hellriegel et al.46 (n = 20 total, 10 ET) | Single session of 40 seconds of continuous theta burst stimulation: 50 Hz, figure of 8 coil, 80% active motor threshold vs. 30% AMT (control intervention) | Primary motor cortex | TRS, accelerometry, MEPs | Improved accelerometry 45 minutes after cTBS, not TRS clinical scores; also real cTBS did not reduce MEP in ET subjects but did in HC |
| Popa et al.42 (n = 22 total, 11 ET) | Five sessions of repetitive cerebellar TMS 1 Hz, figure of 8 coil, daily×5 days, 90% resting motor threshold, 900 pulses over 15 min, to each cerebellar hemisphere | Cerebellar lobule VIII (neuronavigated) | TRS | TRS total improved by 23% at day 29 |
| Gironell et al.48 (n = 10 ET) | Transcranial direct current stimulation (tDCS): 2 cathodal electrodes (25 cm2), 2 mA×20 minutes, 10 consecutive sessions | Both cerebellar hemispheres, 3 cm lateral to the inion | TRS, accelerometry, disability rating scale | No change at day 1, day 10 or day 40 in either TRS or accelerometry |
| Bologna et al.47 (n = 27 total, 16 ET) | Single session cerebellar continuous theta burst stimulation: 50 Hz stimulation repeated 5 Hz over 40 seconds at 80% of active motor threshold, figure 8 coil | 3 cm lateral and 1 cm below the inion | Cortical excitability, tremor frequency, tremor amplitude | Cerebellar cTBS reduced MEPs in HC but not ET cohort Intervention had no effect on TRS, tremor frequency or smoothness of reaching movements |
| Badran et al.44 (n = 10 ET) | 15 daily sessions of 1 Hz rTMS to pre-SMA, butterfly coil for 20 minutes each; sham-controlled | Halfway between Fz and FCz | TRS | 23% reduction in TRS vs 18% reduction in sham-TMS |
| Helvaci Yilmaz et al.49 (n = 6 ET) | 10 daily weekday sessions of anodal tDCS to the dorsolateral prefrontal areas and inion at 2 mA for 20 minutes + 5 more tDCS sessions as above, delivered every other day after 30 days from initial intervention | Prefrontal areas (Fz and C4) | TETRAS motor and ADL rating scales | Statistically significant difference in TETRAS-motor 20% and TETRAS-ADL 17% at 50 days compared to pre-intervention baseline |