Translingual Neurostimulation for the Treatment of Chronic Symptoms Due to Mild-to-Moderate Traumatic Brain Injury

Abstract

Objective To compare the efficacy of high- and low-frequency noninvasive translingual neurostimulation (TLNS) plus targeted physical therapy (PT) for treating chronic balance and gait deficits due to mild-to-moderate traumatic brain injury (mmTBI). Design Participants were randomized 1:1 in a 26-week double-blind phase 1/2 study (NCT02158494) with 3 consecutive treatment stages: in-clinic, at-home, and no treatment. Arms were high-frequency pulse (HFP) and low-frequency pulse (LFP) TLNS. Setting TLNS plus PT training was initiated in-clinic and then continued at home. Participants Participants (N=44; 18-65y) from across the United States were randomized into the HFP and LFP (each plus PT) arms. Forty-three participants (28 women, 15 men) completed at least 1 stage of the study. Enrollment requirements included an mmTBI ≥1 year prior to screening, balance disorder due to mmTBI, a plateau in recovery with current PT, and a Sensory Organization Test (SOT) score ≥16 points below normal. Interventions Participants received TLNS (HFP or LFP) plus PT for a total of 14 weeks (2 in-clinic and 12 at home), twice daily, followed by 12 weeks without treatment. Main Outcome Measures The primary endpoint was change in SOT composite score from baseline to week 14. Secondary variables (eg, Dynamic Gait Index [DGI], 6-minute walk test [6MWT]) were also collected. Results Both arms had a significant ( P <.0001) improvement in SOT scores from baseline at weeks 2, 5, 14 (primary endpoint), and 26. DGI scores had significant improvement ( P <.001-.01) from baseline at the same test points; 6MWT evaluations after 2 weeks were significant. The SOT, DGI, and 6MWT scores did not significantly differ between arms at any test point. There were no treatment-related serious adverse events. Conclusions Both the HFP+PT and LFP+PT groups had significantly improved balance scores, and outcomes were sustained for 12 weeks after discontinuing TLNS treatment. Results between arms did not significantly differ from each other. Whether the 2 dosages are equally effective or whether improvements are because of provision of PT cannot be conclusively established at this time.

Brain Vital Signs Detect Cognitive Improvements During Combined Physical Therapy and Neuromodulation in Rehabilitation From Severe Traumatic Brain Injury: A Case Report

“…Briefly, TG underwent intensive PT-only through 2018 to establish a baseline and then began the 14-week PT + TLNS treatment phase. The PT + TLNS treatment phase was adapted from prior TLNS clinical trial methodology for TBI (Tyler et al, 2019 ; Ptito et al, 2020 ). Brain vital signs data were acquired in parallel for the three baseline time points (B1, B2, B3) and two treatment time points (T4 and T5).…”

“…The stimulation is hypothesized to modulate global brain function through the bottom-up brainstem and cerebellar pathways, augmenting neuroplasticity (Herrick and Keifer, 1998 ; Buisseret-Delmas et al, 1999 ; Marano et al, 2005 ; Wildenberg et al, 2011 ; Frehlick et al, 2019 ). Prolonged stimulation in combination with PT has generated a range of improvements, including improved gait and balance in individuals who have survived TBI (Leonard et al, 2017 ; Bastani et al, 2018 ; Danilov and Paltin, 2018 ; Tyler et al, 2019 ; Ptito et al, 2020 ).…”

Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: A high-density MEG case study

“…When paired with intensive physiotherapy (PT) in a multi-centre clinical trial, TLNS stimulation at both high-and low-frequency stimulation levels resulted in significant balance and gait improvements in mild-to-moderate TBI patients, with previous chronic refractory impairments (21,22). Subsequent examination of high-and low-frequency TLNS levels using high-density electroencephalography (EEG), healthy control, within-subjects, cross-over design, showed significant increases in alpha, theta, and attention-related spatial activity as well as a secondary intensity level exposure effect (23).…”

Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: A high-density MEG case study

“…When paired with intensive physiotherapy (PT) in a multi-centre clinical trial, TLNS stimulation at both high-and low-frequency stimulation levels resulted in signi cant balance and gait improvements in mildto-moderate TBI patients, with previous chronic refractory impairments (21,22). Subsequent examination of high-and low-frequency TLNS levels using high-density electroencephalography (EEG), healthy control, within-subjects, cross-over design, showed signi cant increases in alpha, theta, and attentionrelated spatial activity as well as a secondary intensity level exposure effect (23).…”

“…Following artefact rejection, data were processed in order to extract activity speci c to the motor task. The analysis focused on activity in the beta range (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). In order to identify the speci c beta frequencies most active during TG's movements, a time-frequency analysis (time locked to the click event and averaged across trials) was performed for each recording session on the electrodes in the contralateral motor area (using a Laplacian spatial lter centered at C3 or C4).…”