Cranial nerve non-invasive neuromodulation improves gait and balance in stroke survivors: A pilot randomised controlled trial

Translingual neurostimulation (TLNS) with adjunct physical rehabilitation is used to treat balance and gait deficits in several chronic neurological conditions. The purpose of this review is to summarize and appraise the evidence currently available on the portable TLNS device and to assess its potential clinical application.

In this narrative review, MEDLINE, EMBASE, Web of Science, and Google Scholar were searched for primary research investigating the use of portable TLNS devices on any neurologic condition. Data were extracted, reviewed, and appraised with respect to study design, conduct, and reporting.

Five randomized controlled trials (RCTs), three quasi-experimental trials, and seven case reports/series were found. Most studies demonstrated improvements in balance and gait deficits secondary to traumatic brain injury and multiple sclerosis, but evidence is also present to a lesser degree for stroke and balance disorder patients. In these studies, the feasibility and safety of TLNS have been convincingly demonstrated. Functional magnetic resonance studies have also suggested a plausible neuroplastic therapeutic mechanism. However, the efficacy of TLNS remains unclear due to bias and confounding within studies, and heterogeneity of results between studies.

TLNS is a promising treatment modality for various chronic neurological conditions that are often refractory to conventional therapy. However, TLNS technology remains largely investigational as high-quality RCTs are still required to elucidate efficacy, optimal dosages, necessary treatment durations, and treatment durability. Further research to develop an appropriate control group is needed for scientifically valid comparisons of TLNS.

Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI).

This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively.

The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p < 0.0005). For the pooled population, the SOT responder rate was 67.2% (p < 0.00005), and there were clinically and statistically significant improvements in SOT composite scores after two and five weeks (p < 0.0005). Both groups had reductions in falls and headache disability index scores. Mean dynamic gait index scores in both groups also significantly increased from baseline at weeks 2 and 5.

Significant improvements in balance and gait, in addition to headaches, sleep quality, and fall frequency, were observed with TLNS plus targeted PT; in participants who had a chronic balance deficit following an mmTBI and had plateaued on prior conventional physiotherapy.

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).

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.

TLNS plus PT training was initiated in-clinic and then continued at home.

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.

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.

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.

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.

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.

Cranial-nerve non-invasive neuromodulation (CN-NINM) through the tongue has been proposed as an adjuvant intervention to improve efficacy of rehabilitation. However, CN-NINM effects have only been explored in multiple sclerosis and stroke populations. In this report we used CN-NINM during a 2-week (2 × 1.5 h sessions daily) physiotherapy program for the rehabilitation of a 57 y/o woman presenting with balance and gait impairments after a surgical resection of a fourth ventricular ependymoma. Clinical and instrumented balance and gait assessments showed improved performance in all tests and without adverse effects This study shows the beneficial effects and feasibility of combined physiotherapy and CN-NINM in this patient.