Abstract
Background:Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor (ET) subjects. However, the mechanism of action of TAPS is unknown. Here, we investigated changes in brain metabolism over three months of TAPS use in ET subjects.Methods:This was an interventional, open label, single group study enrolling 5 ET subjects. They received 40 minutes of TAPS treatment twice daily for 90 days. Brain metabolic activity and tremor severity were measured using 18F-fluorodeoxyglucose (FDG) PET/CT, and the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), respectively, at baseline and after 90 days. Tremor power and frequency was measured before and after all TAPS sessions using an onboard three-axis accelerometer.Results:FDG PET/CT revealed areas of hypermetabolism in ipsilateral cerebellar hemisphere and hypometabolism in contralateral cerebellar hemisphere following 90 days of TAPS treatment, compared to day one (uncorrected p value <0.05). Paired pre-post kinematic measurements over 90 days showed significantly decreased tremor power (p < 0.0001) but no change in tremor frequency. The TETRAS score on day 1 decreased from 6.5 ± 2.5 to 4.1 ± 1.8 following TAPS (p = 0.05). The pre-post TETRAS scores on day 90: 4.9 ± 1.5 and 4.1± 1 were lower than pre-TAPS TETRAS score on day 1 (p = 0.14 and 0.05, respectively).Conclusions:Our results suggest that longitudinal TAPS of the median and radial nerves modulates brain metabolism in areas instrumental to motor coordination and implicated in ET. Clinically, TAPS reduced tremor power, but had no effect on tremor frequency. This study paves the way for comprehensive studies in larger cohorts to further elucidate the mechanism of TAPS.Highlights:Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor subjects. Longitudinal TAPS therapy alters cerebellar metabolism, which can be a cause or consequence of tremor reduction. Cerebellar-premotor region connectivity may play a role in the anti-tremor effects of TAPS.
Highlights
Essential tremor (ET) is the most common movement disorder, affecting an estimated 7 million Americans [1]
Positron Emission Tomography (PET) imaging revealed two clusters of increased glucose metabolism in the ipsilateral cerebellar hemisphere and one cluster of reduced glucose metabolism in the contralateral cerebellar hemisphere (p < 0.05, uncorrected) at day 90 compared to day 1 (Figure 1A, C and E, Table 2)
Longitudinal transcutaneous afferent patterned stimulation (TAPS) therapy modulates cerebellar metabolism Our preliminary results demonstrate clusters of increased metabolism in the cerebellar hemisphere ipsilateral to the side of stimulation and a hypometabolic region in the contralateral cerebellar hemisphere following 90 days of TAPS therapy (p < 0.05, uncorrected, Figure 1A, C and E)
Summary
Essential tremor (ET) is the most common movement disorder, affecting an estimated 7 million Americans [1]. While effective [9,10,11,12,13,14], these interventions Scale (TETRAS), a subscale version that included upper are associated with the general risks of surgery, as well as limb tremor assessment and the Archimedes spiral drawing stimulation-induced adverse effects (e.g., paresthesia, dysto- task was conducted (details in tremor severity assessment nia, dysarthria, gait disturbances) [14,15,16]. Non-invasive peripheral nerve stimulation, referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor (ET) subjects. Brain metabolic activity and tremor severity were measured using 18F-fluorodeoxyglucose (FDG) PET/CT, and the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), respectively, at baseline and after 90 days. Highlights: Non-invasive peripheral nerve stimulation, referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor subjects. Cerebellar-premotor region connectivity may play a role in the anti-tremor effects of TAPS
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