There are three main types of stroke:
1.Ischemic stroke: This is the most common type of stroke. A blood clot prevents blood and oxygen from reaching the brain.
2.Hemorrhagic stroke: This occurs when a weakened blood vessel ruptures and normally occur as a result of aneurysms or arteriovenous malformations (AVMs).
3.Transient ischemic attacks (TIAs): Also referred to as a mini-stroke, these occur after blood flow fails to reach part of the brain. Normal blood flow resumes after a short amount of time, and symptoms cease.
The different types of stroke have different causes. However, stroke is more likely to affect people if they have the following risk factors:
1.being overweight
2.being aged 55 years or older
3.a personal or family history of stroke
4.an inactive lifestyle
5.a tendency to drink heavily, smoke, or use illicit drugs
The main symptoms of stroke are:
1.confusion, including trouble with speaking and understanding
2.a headache, possibly with altered consciousness or vomiting
3.numbness or inability to move parts of the face, arm, or leg, particularly on one side of the body
4.vision problems in one or both eyes
5.trouble walking, including dizziness and lack of co-ordination
6.bladder or bowel control problems
7.depression
8.pain in the hands and feet that gets worse with movement and temperature changes
9.paralysis or weakness on one or both sides of the body
10.trouble controlling or expressing emotions
LLLT for Stroke and Brain Injury
Perhaps the most well-investigated (in animal models) application of PBM to the brain lies in its possible use as a treatment for acute stroke. In one series of human clinical trials, PBM significantly improved outcomes in stroke patients.
In the first clinical trial, PBM was applied within 24 hours of a stroke and the study noted statistically significant improvements when administered at 18 hours post-stroke, over the entire surface of the head regardless of the type of stroke. Only one laser treatment was administered, and results were present 5 days later. At 90 days post-stroke, 70 percent of the patients treated with LLLT still showed a significantly successful outcome.
A second clinical trial determined LLLT treatment to be effective for moderate to severe strokes, but not severe. The third clinical trial was inconclusive for any significant results. There is some evidence to suggest that the time between the occurrence of a stroke and initiation of the PBM treatment may be an important factor.
PBM is proving helpful in brain injury recovery in numerous studies. In experiments with mice. those treated with LLLT had significantly reduced neurological deficits, including smaller loss of cortical tissue, better mobility, less depression and anxiety, increased BDNF, and better learning and memory.
In one small study with humans having TBIs ranging from 10 months to 8 years old, application of red and near infrared light emitting diodes (LED) three times a week for 10 minutes over six weeks significantly improved executive function, verbal learning, free recall, sleep, and decreased PTSD symptoms.
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.
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.
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.
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.
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.
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.
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.
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.
“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.”
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.
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.
Peripheral Nere 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.
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.
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.
