Infrared Laser Therapy for Ischemic Stroke: A New Treatment Strategy Results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1)
ABSTRACT The NeuroThera Effectiveness and Safety Trial-1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke.
This was a prospective, intention-to-treat, multicenter, international, double-blind, trial involving 120 ischemic stroke patients treated, randomized 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 measured by National Institutes of Health Stroke Scale (NIHSS) scores of 7 to 22 were included. 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, 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.
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 as 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).
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.
- SourceAvailable from: Sivaraman Purushothuman
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- "There is now a wealth of data from animal models demonstrating that photobiomodulation with low-level near infrared to infrared light (NIr, 600–1000 nm) is neuroprotective. For example , NIr treatment has yielded beneficial outcomes in models of retinal damage  , traumatic brain injury   , Parkinson's disease     and Alzheimer's disease (AD)   and in clinical trials on patients suffering macular degeneration  and stroke . We have previously shown, in two transgenic mouse models, that one month of transcranial NIr treatment mitigates the pathology of cerebral cortex that characterises AD . "
ABSTRACT: We previously reported that Alzheimer-related pathology in cerebral cortex of APP/PS1 and K3 tau transgenic mouse strains is mitigated by near infrared light (NIr). Here, we extend these observations to the cerebellum. One month of NIr treatment mitigated the deposition of β-amyloid in cerebellar cortex of APP/PS1 mice, and the formation of neurofibrillary tangles, the hyperphosphorylation of tau, the damage caused by oxidative stress and the downregulation of cytochrome oxidase expression by Purkinje cells in the cerebellar cortex of K3 mice. These findings show the ability of NIr to mitigate degeneration in many - probably all - regions of the mouse brain. Copyright © 2015. Published by Elsevier Ireland Ltd.Neuroscience Letters 02/2015; 591. DOI:10.1016/j.neulet.2015.02.037 · 2.03 Impact Factor
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- "These interventions upregulate endogenous mechanisms of cellular repair, some identified at the mitochondrial level, and reduce neural degeneration in models of parkinsonism, dementia, and macular degeneration. In clinical trials, dietary saffron has been reported    to restore vision partially and to stabilize the macular region of retina in age-related macular degeneration; transcranial infrared radiation has been reported to reduce functional deficit after stroke , and direct infrared radiation to mitigate age-related macular degeneration  ; and remote ischemic preconditioning is under trial in stroke, cervical myelopathy, and subarachnoid hemorrhage  . With all techniques, larger trials and more development of the interventions must follow , but it is remarkable that the brain and retina can be protected or, more accurately, can be induced to self-protect, by a range of low-impact interventions. "
ABSTRACT: This review traces evidence that age-related dementia (Alzheimer's disease) results from the destructive impact of the pulse on cerebral vasculature. Evidence is reviewed that the neuropathology of the dementia is caused by the breakdown of small cerebral vessels (silent microbleeds), that the microbleeds result from pulse-induced damage to the cerebral vessels, and that pulse becomes increasingly destructive with age, because of the age-related stiffening of the aorta and great arteries, which causes an increase in the intensity of the pressure pulse. Implications for therapy are discussed, and evidence is reviewed that pulse-induced destruction of the brain, and of another highly vascular organ, the kidney, are becoming the default forms of death, the way we die if we survive the infections, cardiovascular disease, and malignancies, which still, for a decreasing minority, inflict the tragedy of early death.Journal of Alzheimer's disease: JAD 10/2014; 44(2). DOI:10.3233/JAD-141884 · 4.15 Impact Factor
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- "In addition, conditions specific to the nervous system have shown improved recovery following R/NIR-IT, including retinal degeneration , , CNS injury and stroke –. Clinical trials are currently underway assessing R/NIR-IT for stroke, with NeuroThera Effectiveness and Safety Trial (NEST)-1 and NEST-2 already completed with some clinical improvement shown , . This has led to the commencement of a third trial (NEST-3). "
ABSTRACT: Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P#0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P#0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P#0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P.0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P.0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.PLoS ONE 08/2014; 9(8). DOI:10.1371/journal.pone.0104565 · 3.23 Impact Factor