Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury

Maria Gabriela Figueiró Longo ,Arman Avesta,Eva Ratai,Anastasia Yendiki,Jacqueline Namati,Terry M Rauch ,Jonathan Welt,Ramon Diaz‐Arrastia ,Jarone Lee,Michael R Hamblin ,Nathaniel D Mercaldo ,Michael H Lev ,Blair A Parry,R.b Anderson ,Suk-Tak Chan,Lynn A Drake ,Isabel Chico‐Calero ,Benjamin J Vakoc ,Can Ozan Tan,Rajiv Gupta

doi:10.1001/jamanetworkopen.2020.17337

Abstract

Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. ClinicalTrials.gov Identifier: NCT02233413.

Highlights

Traumatic brain injury (TBI), a major cause of death and disability, is a significant public health problem in the US and worldwide.[1,2,3] Traumatic brain injury is defined as an external force-induced injury that may impair normal brain functions, such as memory, movement, sensation, and emotions
Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: −0.018; 95% CI, −0.026 to −0.010; P < .001).The level light therapy (LLLT) group had lower Rivermead Post-Concussion Questionnaire (RPQ) scores, but this effect did not reach statistical significance
Effect of Transcranial Low-Level Light vs Sham Therapy Among Patients With Traumatic Brain Injury. In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events

Summary

Introduction

Traumatic brain injury (TBI), a major cause of death and disability, is a significant public health problem in the US and worldwide.[1,2,3] Traumatic brain injury is defined as an external force-induced injury that may impair normal brain functions, such as memory, movement, sensation, and emotions Such impairments, which are generally underrated and underreported, may have highly variable clinical presentation.[4] Traumatic axonal injury is one of the primary pathophysiologic consequences of impact and acceleration injuries to the brain.[5] White matter tracts are vulnerable to such injury, which may manifest as chemical and mechanical changes in the affected neurons. While these changes could trigger cell apoptosis and consequent neural disconnection, they may resolve, leading to partial remyelination or even full recovery.[6,7] therapies that can induce recovery of myelin in axons after head trauma have been a target of research for several years.[8]

Objectives

Methods

Results

Discussion

Conclusion