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11 Articles in Volume 10, Issue #8
A Neuro-geometric Basis for Pain Management
Brain Reorganization with Severe Pain: New Understanding and Challenges
Chronic Migraine: An Interactive Case History, Part 2
Diagnosing and Managing Chronic Ankle Instability
High Potency Ultrasound for the Treatment of Connective Tissue Disorders
Intranasal Naloxone for At-home Opioid Rescue
Misuse of ‘Hyperalgesia’ to Limit Care
Neurological Effects of Therapeutic Laser
Preventive Medications For Headache
Psychological Wounds of Trauma and Motor Vehicle Accidents
Treat the Pain... Save a Heart

Neurological Effects of Therapeutic Laser

The rehabilitative possibilities of therapeutic laser are encouraging and continuing studies of the underlying mechanism of action and biologic effects will likely result in improved outcomes for the neurologic patient.

One of the areas of laser therapy that is rather interesting and promises significant potential for healing is application of therapeutic laser to neurological conditions. In this article, I will present a review of scientific studies relative to neurological effects of laser and discuss some of the more promising applications.

Therapeutic laser has been studied for numerous neurological conditions that include:

  • Stroke (including acute embolic stroke, ischemic stroke)
  • Traumatic brain injury
  • Neurodegenerative diseases such as Parkinson’s Disease
  • Trigeminal neuralgia
  • Post-herpetic neuralgia (PHN)
  • Cerebral palsy
  • Spinal cord injuries
  • Peripheral nerve regeneration
  • Major depression

Stroke

Lapchak et al applied infrared light therapy to rabbits that suffered acute embolic stroke. Light therapy was applied transcranially 6 to 12 hours post embol-ization with continuous wave and pulsed waves. Behavior analysis was performed 48 hours after ischemic stroke. The results demonstrated that the pulsed mode IR light therapy resulted in significant clinical improvement when administered 6 hours following embolic strokes in rabbits.1

Oron et al studied the effects of GaAs laser irradiation on adenosine triphosphate (ATP) production in normal human neural progenitor cells. Tissue cultures were treated with the GaAs laser and ATP levels were determined at 10 minutes post laser application. The quantity of ATP in the treated cells was significantly higher than the non-treated group. The application of laser to normal human neuronal progenitor (NHNP) cells significantly increases ATP production. This may explain the beneficial effects of LLLT in stroked rats.2

Naeser studied the effect of laser acupuncture to treat paralysis in stroke patients and to examine the relationship between anatomical lesion sites on CT scan and the potential for improvement following laser acupuncture treatments. Seven stroke patients (five men and two women; aged 48 to 71) were admitted to the study. Five cases had a single left hemisphere stroke and two cases had a single right hemisphere. Five patients were treated for residual arm or leg paralysis. They exhibited greatly reduced arm and leg power with greatly reduced or absent voluntary isolated finger movement. Two cases, with good arm and leg power but exhibiting mildly reduced isolated finger movement, were treated only for hand paresis.

CT scans were obtained on all patient at least three months post stroke. Six patients began receiving the laser acupuncture treatments during the chronic phase post stroke (10 months to 6.5 years). These intervals are beyond the spontaneous recovery period of up to six months post stroke.3,4 One hand paresis case began receiving treatments during the acute phase post stroke (one month post stroke). Because all but one patient were beyond the spontaneous recovery period, each patient served as his/her own control. No sham laser treatments were administered. None of the stroke patients was receiving physical therapy or occupational therapy treatments during the course of the laser acupuncture treatments. The use of low-level laser for long-term treatment is especially desirable for chronic stroke patients with hand paresis. The patient can be trained to treat him/herself at home, using an inexpensive 5mW red-beam diode laser pointer and a microamps TENS device.

This is the first study to examine the effect of low-level laser therapy on acupuncture points to treat paralysis in stroke patients where the lesion location was known for each patient. Results suggest that low-level laser therapy on acupuncture points is effective to help reduce the severity of paralysis in stroke patients—especially those with mild-to-moderate paralysis. The treatments should be initiated as soon as possible post stroke, even within 24 hours post stroke. A comprehensive rehabilitation program of physical therapy, occupational therapy, plus needle and/or laser acupuncture is recommended.5

Lampi et al conducted a prospective, intention-to-treat, multicenter, international, double-blind trial (Neurothera® Effectiveness and Safety Trial-1; NEST-1) involving 120 ischemic stroke patients treated, randomized in a 2:1 ratio, with 79 patients in the active treatment group and 41 in the sham (placebo) control group. Only patients with baseline stroke severity scores of 7 to 22 were included, as measured by the National Institutes of Health Stroke Scale (NIHSS). Patients who received tissue plasminogen activator were excluded. Outcome measures were the patients’ scores on the NIHSS, modified Rankin Scale (mRS), Barthel Index, and Glasgow Outcome Scale at 90 days after treatment.

The primary outcome measure, prospectively identified, was successful treatment as documented by NIHSS. This was defined as a complete recovery at day 90 (NIHSS 0 to 1), or a decrease in NIHSS score of at least 9 points (day 90 versus baseline) and was tested as a binary measure (bNIH). Secondary outcome measures included mRS, Barthel Index, and Glasgow Outcome Scale. Primary statistical analyses were performed with the Cochran-Mantel-Haenszel rank test, stratified by baseline NIHSS score or by time to treatment for the bNIH and mRS. Logistic regression analyses were conducted to confirm the results.

“A post-hoc analysis of 434 patients who suffered moderate to moderately severe strokes showed a favorable outcome in 51.6% of patients in the TLT group compared to 41.9% of patients in the sham group. This 9.7% treatment effect was statistically significant (p-value 0.044).”

Mean time to treatment was >16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%) as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days with a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS (“shift in Rankin”) score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs).6

The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.

Zivin et al performed a double-blind, sham-controlled (placebo) trial (NEST-2) which enrolled 660 patients. Patients were eligible for inclusion in the study if they were 40-90 years of age, had moderate to severe strokes, and had not received tissue plasminogen activator (tPA). Initiation of treatment had to occur within 24 hours after stroke onset.

In NEST-2, TLT achieved a favorable outcome in 36.3% of patients compared to only 30.9% of patients in the sham group (p-value 0.094). The primary efficacy endpoint was a favorable 90-day score of 0-2 using the modified Rankin Scale (mRS). Mortality rates and serious adverse events (SAEs) did not differ between groups, providing further evidence of the safety of TLT.

A post-hoc analysis of 434 patients who suffered moderate to moderately severe strokes showed a favorable outcome in 51.6% of patients in the TLT group compared to 41.9% of patients in the sham group. This 9.7% treatment effect was statistically significant (p-value 0.044).

“TLT is one of the most promising new therapies that we’ve seen in a long time, especially as it may expand the treatment window for ischemic stroke to 24 hours. We look forward to commencing NEST-3 to further investigate TLT,” stated Professor Werner Hacke, MD, PhD, Chairman of Neurology at the University of Heidelberg, who will join Professor Zivin as Co-Chairman of the NEST-3 Steering Committee.7

Traumatic Brain Injury

Oron et al, in another study, evaluated the use of LLLT as a potential therapy for traumatic brain injury (TBI) utilizing a rat model. TBI was induced by a weight–drop device. Motor function was assessed one hour post trauma using a neurological severity score (NSS). The mice were divided into three groups of eight each: a control, and two laser groups, one receiving 10 mW/cm2 and one receiving 20 mW/cm2 transcranially. A GaAs laser was used four hours post trauma to illuminate the entire cortical area of the brain. No significant changes were seen in the neurological soft signs (NSS) from 24 to 48 hours. There were significantly lower scores in the laser treated groups from days 5 to 28. The results suggest that a non-invasive transcranial application of laser therapy given four hours post TBI provides significant long-term neurological benefit.8

Rockhind et al performed a study on the effect of 780 nm laser irradiation on the growth of embryonic rat brain cultures embedded in NVR-Gel (cross-linked hyaluronic acid with adhesive molecule laminin and several growth factors). Dissociated neuronal cells were first grown in suspension attached to cylindrical micro-carriers (MCs). The formed floating cell-MC aggregates were subsequently transferred into stationary cultures in gel and then laser treated. The response of neuronal growth following laser irradiation was investigated. The 780 nm laser irradiation accelerated fiber sprouting and neuronal cell migration from the aggregates. Furthermore, unlike control cultures, the irradiated cultures (mainly after a one minute irradiation of 50 mW) were already established after a short time of cultivation. They contained a much higher number of large size neurons (P<0.01), which formed dense branched interconnected networks of thick neuronal fibers.

They concluded that 780 nm laser phototherapy of embryonic rat brains cultures, embedded in hyaluronic acid-laminin gel and attached to positively charged cylindrical MCs, stimulated migration and fiber sprouting of neuronal cells aggregates and developed large size neurons with dense branched interconnected network of neuronal fibers. This modality can therefore be considered as potential procedure for cell therapy of neuronal injury or disease.9

Parkinson’s Disease

Trimmer et al performed an in vitro study that showed a single, brief treatment with a GaAlAs laser increased the velocity of mitrochondrial movement for two hours in cells taken from patients with sporadic Parkinson’s Disease (PD). This accelerated the velocity up to levels approximating those of disease free age-matched cells. Their findings provide early stage confirmation that laser therapy has the potential to improve neuronal function in many patients with PD and other neurodegenerative diseases.3

Trigeminal Neuralgia

Eckerdal and Lehmann performed a double-blind, placebo controlled study with low intensity laser therapy on patients with trigeminal neuralgia. Two groups of patients, one with 14 subjects and the other with 16 subjects, were studied. The results showed that in the active laser treatment group of 16, ten were completely pain free, two had less pain, and four had little or no change in pain. Six of these patients had continued relief at one year post treatment.

The placebo-treated group had one person who was pain free, four had less pain and the remaining nine had little or no relief. After one year only one person was pain free. The researchers concluded that the study demonstrated that LLLT treatment is an effective method and excellent supplement to conventional therapies used in the treatment of trigeminal neuralgia.4

Post-Herpetic Neuralgia

Kemmotsu et al performed a double blind study utilizing low-level laser therapy (LLLT) for the treatment of post-herpetic neuralgia (PHN). Sixty-three patients were evaluated (25 males and 38 females with an average age of 69 years). A double blind assessment of LLLT was also performed in 12 PHN patients. A GaAlAs laser with a continuous output of 60 mW was used. Pain scores were obtained via the visual analogue scale (VAS). There was very good (VAS<3) immediate pain reduction after the first treatment in 26 and good relief (VAS 7-4) in 30 patients. The long term effects of LLLT was no pain (VAS 0) in 12 patients and slight pain (VAS 1-4) in 46 patients. The researchers concluded that LLLT is a useful modality for pain attenuation in PHN patients and, because LLLT is non-invasive, painless and safe.10

Toshikazu et al performed a study to evaluate the effects of laser irradiation (LLLT) in the area near the stellate ganglion on regional skin temperature and pain intensity in patients with postherpetic neuralgia. A double blind, crossover and placebo-controlled study was de-signed. Eight inpatients (six male, two female) receiving laser therapy for pain attenuation were enrolled in the study after institutional approval and informed consent. Each patient received three treatment sessions on separate days in a randomized fashion. Three minutes irradiation with a 150 mW laser (session one), three minutes irradiation with a 60 mW laser (session two), and three minutes placebo treatment without laser irradiation.

Neither the patient nor the therapist was aware which session type was being applied until the end of the study. Regional skin temperature was evaluated by thermography of the forehead and pain intensity was recorded using a visual analogue scale (VAS). Measurements were performed before treatment, immediately after then at 5, 10, 15, and 30 minutes after treatment. Regional skin temperature increased following both 150 mW and 60mW laser irradiation, whereas no changes were obtained by placebo treatment. VAS decreased following both 150 mW and 60 mW laser treatments, but no changes in VAS were obtained by placebo treatment. These changes in the temperature and VAS were further dependent on the energy density (i.e., the dose).

Results demonstrate that laser irradiation near the stellate ganglion produces effects similar to a stellate ganglion block. The results clearly indicate that they were not placebo effects but true effects of laser irradiation.11

Cerebral Palsy

Anwar et al conducted a study at Anwar Shah’s First Cerebral Palsey and Paralysis Clinic and Research Center in collaboration with the Departments of Neurology and Neurosurgery, Children Hospital Lahore, Pakistan, to evaluate the effects of aculaser therapy (laserpuncture) in children suffering from cerebral palsy and associated neurological disorders like epilepsy, cortical blindness, spasticity, hemiplegia, paraplegia, quadriplegia, paraplegia, monoplegia, sensory-neural deafness and speech disorders. One hundred children were treated and the data were gathered during a period of 18 months from December 2003 till June 2005. The treatment of the children lasted a minimum of six weeks and a minimum of ten treatment sessions. Those children who were given a break from treatment for 4 to 12 weeks did not show any reversal of symptom relief.

Analysis of the data showed the following results12:

  • 69 out of 81 children with spasticity and stiffness (85%) showed a marked improvement.
  • Significant reduction in intensity, frequency, and duration of epileptic activity was observed in 34 out of 54 children (63%).
  • There was improvement in 13 out of 18 children with cortical blindness (72%).
  • 31 out of the 45 children with hearing difficulties marked improvement (69%).
  • 67 out of 100 children with speech disorders showed improvement (67%).
  • 32 out of 46 children with hemiplegia showed improvement in movement, muscle tone, and power (69%).
  • 25 out of 36 children with quadriplegia showed improvement in gross and fine muscle function (69%).
  • 12 out of 18 children with lower body paraplegia showed improvement in weight bearing capabilities, standing, and movement (67%).

Spinal Cord Injuries

Wu et al performed a study on rats utilizing a 810 nm GaAlAs laser with a 150 mW output to treat spinal cord injuries (SCI) following creation of a contusion model and a dorsal hemi-section model. Light was applied transcutaneously at the lesion site immediately after injury and daily for 14 consecutive days. The daily dose at the skin overlying the lesion was 1589 J/cm2 (0.3 cm2 spot area for 2997 seconds). Mini-ruby was used to label corticospinal tract axons. These were counted and measured from the lesion site distally. Functional recovery was assessed by footprint test for the hemi-section model and open-field test for the contusion model. The rats were euthanized three weeks after injury. The average length of axonal regrowth in the group of rats treated with the laser was 6.89 +/- 0.96 in the hemi-section group and 7.04 +/- 0.76 in the contusion group as compared with the untreated control group of 3.66 +/- 0.26 in the hemi-section group and 2.89 +/- 0.84 in the contusion group.

 

The total axon number in the LT groups was significantly higher compared to the untreated groups for both injury models (P<0.05). For the hemi-section model, the LT group had a statistically significant lower angle of rotation (P<0.05) compared to the controls. For contusion model, there was statistically significant functional recovery (P<0.05) in the LT group compared to untreated control. It is concluded that light therapy, applied non-invasively, promotes axonal regeneration and functional recovery in acute SCI caused by different types of trauma. These results suggest that light is a promising therapy for human SCI.13

“Rochkind…study shows that low power laser irradiation can progressively improve peripheral nerve function in long-term peripheral nerve injured patients, leading to significant functional recovery.”17

Byrnes et al performed a study aiming to demonstrate the photobiomodulation (PBM) effects of 810 nm GaAlAs laser as a potential therapy for the treatment of spinal cord injuries (SCI). They aimed at demonstrating that the laser could penetrate deeply into the body and promote neuronal regeneration and functional recovery. Adult rats underwent a T9 dorsal hemisection followed by treatment with an 810 nm, 150 mW diode laser (dosage = 1,589 J/cm²). Axonal regeneration and functional recovery were assessed using single and double label tract tracing and various locomotor tasks. The immune response within the spinal cord was also assessed. PBM, with a 6% power penetration to the spinal cord depth, significantly increased axonal number and distance of regrowth (P < 0.01). PBM also returned aspects of function to baseline levels and significantly suppressed immune cell activation and cytokine/chemokine expression. The authors concluded that their results demonstrate that light, delivered transcutaneously, improves recovery after injury and suggests that light will be a useful treatment for human SCI.14

Byrnes et al studied secondary injury in the spinal cord which results in axonal degeneration, scar and cavity formation and cell death around the site of initial trauma and is a primary cause for the lack of the axonal regeneration observed after spinal cord injury (SCI). The immune response after SCI is under investigation as a potential mediator of secondary injury. Treatment of SCI with 810 nm LLLT suppresses the immune response and improves axonal regeneration. This study demonstrated that LLLT has an anti-inflammatory effect on the injured spinal cord, and may reduce secondary injury, thus providing a possible mechanism by which light therapy may result in axonal regeneration.15

Peripheral Nerve Regeneration

Midamba and Haanaes performed a study on peripheral nerve regeneration in humans. Forty patients with short and long term neuro-sensory impairment following perioral nerve injuries were chosen for the study. Assessment of their sensory level was undertaken using a variety of nerve tests. One of them was a visual analogue scale (VAS) for registration of sensitivity level prior to and after 10 treatment sessions and additionally for 21 of the 40 patients after 20 treatment sessions. Low level laser therapy (LLLT) was applied using GaAlAs 830 nm, 70 mW continuous wave. A dose of 6.0 J/cm² was standardized for all patients. Improvement of the eight patients with clinical symptoms of less than one year was between 40-90% (average 51.9%) after 10 treatments and between 50-80% (average 66.7%) after 20 treatments for the three patients who continued with the treatment. In 32 of the 40 patients with clinical symptoms of more than one year duration, their improvement was estimated at between 40 and 80% (average 54.8%). Of the 21 patients who completed 20 treatment sessions, the end results were between 60% and 90% (average 71.1%). This was an uncontrolled clinical study of LLLT on perioral nerve injuries and demonstrated the effectiveness of GaAlAs laser when applied to the nerve trunk and terminal endings. Although controlled research into actual mechanisms and pathways is needed, the preliminary findings are very promising.16

Rochkind performed a clinical, double-blind, placebo-controlled randomized study to measure the effectiveness of laser phototherapy on patients who have been suffering from incomplete peripheral nerve and brachial plexus injuries for six months up to several years. This study shows that low power laser irradiation can progressively improve peripheral nerve function in long-term peripheral nerve injured patients, leading to significant functional recovery. Recently, biodegradable composite transplants—based on cell tissue-engineering technology—were used for the treatment of complete peripheral nerve and spinal cord injury in rats. The laser phototherapy was applied as a supportive factor for accelerating and enhancing axonal growth and regeneration after reconstructive peripheral nerve and spinal cord procedures. The significance of this innovative methodology will be the provision of a new nerve tissue-engineering modality and laser technology for treatment of complete peripheral nerve and spinal cord injury.17

Rockhind et al also performed a series of experimental studies to evaluate the efficacy of low power laser irradiation as a supportive factor for accelerating and enhancing axonal growth and regeneration after reconstructive peripheral nerve and spinal cord procedures. In these procedures, regenerative and reparative biotechnological sources were used for the microsurgical reconstruction. These re-search projects are an interdisciplinary effort of a novel therapeutic strategy where a biodegradable nerve tube was used for peripheral nerve reconstruction and composite implants of cultured embryonal nerve cells were applied for a transected spinal cord followed by post-operative laser treatment.

In addition, the studies investigated the role of low power laser irradiation in accelerating and enhancing axonal growth in a nerve cell culture model and primary repair of injured peripheral nerve. The significance of these approaches will be the provision of new nerve tissue-engineering modality and laser technology for treatment of severe peripheral nerve and spinal cord injury.18

Anders and Backs have previously shown that LLLT increases the rate of facial nerve regeneration and alters choline acetyltransferase immunoreactivity during regeneration of crushed rat facial nerves and increases mRNA for a calcitonin gene-related peptide after facial nerve transection. These findings indicate that LLLT optimizes nerve regeneration. The purpose of this study was to quantitatively determine if LLLT can rescue motoneurons after transection of the facial nerve. A 633 nm laser 8.5 mW laser was used for 90 minutes for 14 days. This was done six to nine months after the nerve injury. The frequency of facial motoneurons that died after axotomy was decreased significantly from 36.45% to 13.30% when the axotomized facial nerves were treated with LLLT. These results suggest that LLLT is a non-invasive therapy for rescue of axotomized neurons and may afford a promising treatment for devastating spinal cord injuries.19

Datsenko studied twenty-three patients aged 23-75 who had ischemic stroke in the carotid basin (up to two years after the acute period of the stroke). The course of magneto-laser therapy (MLT) lasted 15 days. The author carried out neurological examination, determined the state of psycho-emotional activity, cerebral hemodynamics, and frequency amplitude indices of the brain to assess the mechanisms of MLT effect on the CNS functional state in patients during a rehabilitative period after ischemic stroke. The course of MLT was found to improve cerebral hemodynamics and increase the level of bioelectrical activity in the brain. Based on the results, we can recommend that MLT be included in the rehabilitation program in patients that have had ischemic stroke.20

Major Depression

Schiffer et al performed a study with 10 patients (five male, five female) with major depression, including nine with anxiety, seven with a past history of substance abuse (six with an opiate abuse and one with an alcohol abuse history), and three with post traumatic stress disorder. The study participants were given a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). They were then given four 4-minute treatments in a random order: Near Infrared Light Radiation (NIR) to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment, the PANAS was repeated. At two weeks and at four weeks post treatment, all 3 rating scales were repeated. During all treatments, total hemoglobin (cHb) as a measure of rCBF was recorded with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain. At two weeks post treatment, 6 of 10 patients had a remission (a score < 10) on the HAM-D and 7 of 10 achieved a score less than or equal to 10 on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at two weeks.

Mean rCBF across hemispheres increased from 0.011 units in the ‘off’ condition to 0.043 units in the ‘on’ condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment, the PANAS improved to a significantly greater extent with NIR ‘on’ relative to NIR ‘off’ when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. No side effects were observed. This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated.21

Conclusion

We can see from the referenced studies that there are a number of beneficial neurological effects arising from the application of therapeutic laser and point to significant implications for therapeutic applications in potentially serious neurological conditions such as stroke, Parkinson’s Disease and cerebral palsy, to name a few. The rehabilitative possibilities are encouraging and should cause us to adjust our concepts and explanation of the mechanisms of many of these neurological conditions including axonal degeneration following spinal cord injury. Therapeutic laser is a low risk clinical approach that could benefit countless numbers of neurological patients. It is expected that as research continues and understanding of the underlying mechanisms improves, we will be able to apply laser therapy more effectively to the neurological patient.

Last updated on: March 7, 2011
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