Role of low-level laser therapy in neurorehabilitation

Abstract

This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, anti-oxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered.

Figure 1

Diagram of the various medical applications of low-level light therapy.

Figure 2

Illustration of mitochondrion, as well as of the electron transport chain and oxidative metabolism.

Figure 3

Complex IV (cytochrome c oxidase) is the principal chromophore involved in low-level light therapy. It has 2 copper centers and 2 heme prosthetic groups. Cytochrome c is oxidized and oxygen is reduced to water during respiration.

Figure 4

Nitric oxide can bind to copper (or heme) centers in cytochrome c oxidase and inhibit respiration. The nitric oxide may be photodissociated by absorption of red or near infrared light, allowing oxygen to return and sharply increasing respiration and adenosine triphosphate formation.

Figure 5

Diagram that illustrates the mechanism of low-level light therapy (LLLT) on the cellular and molecular level. Near infrared light, absorbed by the mitochondria, causes upregulation of the cellular respiratory chain. A host of downstream cellular responses involving nitric oxide, reactive oxygen species, and cyclic adenosine monophosphate ensues, which ultimately dictates LLLT effects.

Figure 6

Location of periventricular white matter (PVWM) area (black arrow), adjacent to the body of the lateral ventricle, located immediately superior to the posterior limb, internal capsule (computed tomography slice angulation, coronal and axial views). An extensive lesion in the PVWM was associated with severe paralysis and poor response following low-level light therapy (LLLT) or needle acupuncture treatments in chronic stroke patients with upper extremity, lower extremity, and hand paralysis. Patients with a lesion that was present in less than half of the PVWM area and who had a lesion that was not adjacent to the body of the lateral ventricle had less severe paralysis and good response after a series of LLLT or needle acupuncture treatments (34,37-39). Chronic stroke patients who had some preserved isolated finger flexion and extension before LLLT had the best potential for improvement after LLLT or needle acupuncture treatment. Other cases often had reduced spasticity after LLLT or needle acupuncture treatments.

Figure 7

(a.) Computed tomography (CT) scan of a 65-year-old woman obtained 5 months after stroke onset shows sparing of the most posterior portion of the periventricular white matter (PVWM) (white arrow), that is, likely sparing of some of the leg fibers. This patient showed improvement in knee flexion (b.) and knee extension (c.) after low-level light therapy (LLLT)-laser acupuncture treatments, which were initiated at 12 months after stroke onset. Knee extension increased from 77%-89% after 40 LLLT treatments, and her ability to climb up and down stairs improved. (She had shown some improvement on lower extremity tests after needle acupuncture treatments applied earlier after her stroke.) No improvement was seen in the upper extremity after LLLT or needle acupuncture, likely because of an extensive lesion in the more anterior portions of the PVWM. The arm paralysis was severe, scoring 0% isolated active range of motion for all arm tests at all times. The improvement in knee flexion and knee extension remained stable at 2 months after the last LLLT-laser acupuncture treatment (15 months after the stroke occurred). (Reprinted with author's permission, [34])

Figure 8

(a.) Before the first low-level laser therapy (LLLT) and microamps transcutaneous electrical nerve stimulation (TENS) acupuncture treatment. It was 1.5 years after stroke onset and the patient still had right hand spasticity and was unable to extend her fingers into full extension. Microamps TENS was applied for 20 minutes to acupuncture point Heart 8 (in the palm of the hand) and Triple Warmer 5 (proximal to the dorsum of the wrist). Red-beam laser (670 nm, 5 mW, 4 J/cm2) was applied to the 6 Jing-Well points, located at base of fingernail beds on the hand, plus a few additional hand points. (b.) Immediately after the first 20-minute LLLT and microamps TENS acupuncture treatment, the patient had less hand spasticity and better control to open the fingers into full extension. More treatments are required for a longer-lasting effect. The patient can treat herself at home by using this LLLT and microamps TENS protocol, which is painless and noninvasive [41]. (c.) and (d.) A similar stroke case is shown.

Figure 9

(a.) Red and near-infrared (NIR) light-emitting diode (LED) cluster head (2-inch diameter) for transcranial LED treatments. (b.) Sample placement location on right forehead for one of the LED cluster heads during transcranial LED treatment. (c.) Graph that shows significant improvement in cognition on tests of Executive Function (inhibition, and inhibition accuracy, +2 SD) after LED treatments in the second patient with chronic, mild traumatic brain injury. The patient returned to full-time employment after 4 months of nightly transcranial LED treatments. (c reprinted with permission, (58).)