Rationale for 1068 nm Photobiomodulation Therapy (PBMT) as a Novel, Non-Invasive Treatment for COVID-19 and Other Coronaviruses: Roles of NO and Hsp70.

Researchers from across the world are seeking to develop effective treatments for the ongoing coronavirus disease 2019 (COVID-19) outbreak, which arose as a major public health issue in 2019, and was declared a pandemic in early 2020. The pro-inflammatory cytokine storm, acute respiratory distress syndrome (ARDS), multiple-organ failure, neurological problems, and thrombosis have all been linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fatalities. The purpose of this review is to explore the rationale for using photobiomodulation therapy (PBMT) of the particular wavelength 1068 nm as a therapy for COVID-19, investigating the cellular and molecular mechanisms involved. Our findings illustrate the efficacy of PBMT 1068 nm for cytoprotection, nitric oxide (NO) release, inflammation changes, improved blood flow, and the regulation of heat shock proteins (Hsp70). We propose, therefore, that PBMT 1068 is a potentially effective and innovative approach for avoiding severe and critical illness in COVID-19 patients, although further clinical evidence is required.

Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition.

Alzheimer's disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer's disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (Aß) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600-1000 nm) was associated with a reduction in the size and number of amyloid-ß plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060-1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation's institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement.

Open-label, short-term, repetitive transcranial magnetic stimulation in patients with Alzheimer's disease with functional imaging correlates and literature review.

BACKGROUND: Accumulating evidence suggests repetitive transcranial magnetic stimulation (rTMS) may be beneficial in ameliorating cognitive deficits in Alzheimer's disease (AD). METHODS: AD patients received four high-frequency rTMS sessions over the bilateral dorsolateral prefrontal cortex (DLPFC) over two weeks. Structured cognitive assessments were administered at baseline, at 2 weeks after completion of rTMS, and at 4 weeks post treatment. At these same times, tolerant patients underwent functional magnetic resonance imaging (fMRI) while performing structured motor and cognitive tasks. We also reviewed literature regarding the effects of rTMS on cognitive function in AD. RESULTS: A total of 12 patients were enrolled, eight of whom tolerated the fMRI. Improvement was seen in Boston Diagnostic Aphasia Examination tests of verbal and non-verbal agility 4 weeks post-treatment. The fMRI analysis showed trends for increased activation during cognitive performance tasks immediately after and at 4 weeks post-treatment. Our literature review revealed several double-blind, sham-controlled studies, all showing sustained improvement in cognition of AD patients with rTMS. CONCLUSIONS: There was improvement in aspects of language after four rTMS treatments, sustained a month after treatment cessation. Our results are consistent with other studies and standardization of treatment protocols using functional imaging may be of benefit.

Restoring cortical connectivity directionality and synchronization is essential to treating disorder of consciousness.

The design of neurorehabilitation therapy to treat subjects with altered consciousness provides opportunities and challenges to professionals involved with the care for these severely ill patients. While there is an increased interest in determining methods to restore consciousness in these patients, the process is complex and challenging, due in part to the diverse aetiology of these states of consciousness, and also to the intricate cerebral connectivity involved in their treatment. The present case study examines a patient who showed signs of emergence from the vegetative state after neurorehabilitation using The Combined Method Therapy (CMT). In this case, neurorehabilitation therapy was applied simultaneously with pharmacological treatment, stimulation, and neuroimaging techniques to help adjust drug dosage. The results of this study suggest that this combined approach to treatment promoted connectivity among posterior and anterior cortical regions aiding emergence from the vegetative state.

Source imaging of QEEG as a method to detect awareness in a person in vegetative state.

BACKGROUND: Assessment of awareness in patients with severe brain injury remains subjective, although patients with even limited awareness (e.g. minimal conscious state, MCS) have different prognoses and treatment than those in vegetative state (VS). Recently, task appropriate differential regional activation in VS has been reported using fMRI during mental imagery. PRIMARY OBJECTIVE: Demonstration of conscious awareness in reproducible differential EEG source localization images in a VS patient reflecting requested mental imagery was performed. METHODS: A VS patient (with re-test) and a normal control were requested to imagine singing and to mentally perform serial subtraction, while EEG was recorded. QEEG source localization was performed to identify regions of brain activation in response to tasks. RESULTS: Replicable distinctive activation of brain areas appropriate for each task was seen in the VS patient and control. Frequency spectra shifted to beta, with significant source activation in regions including the bilateral anterior cingulate, insula, left caudate and dorsolateral pre-frontal cortex to singing and the putamen, insula, left pre-frontal cortex and right temporal gyrus to subtraction by 7's. CONCLUSIONS: Results from this single case suggests the potential utility of QEEG source localization images to detect awareness in patients clinically diagnosed as being in VS. This indicates the possibility that EEG may serve as an important adjunct to the assessment of awareness in patients with disorders of consciousness in the clinical setting.

A pilot study of mind-body changes in adults with asthma who practice mental imagery.

CONTEXT: Despite the growing number of studies of imagery and the use of complementary and alternative modalities as treatments for asthma, research on mental imagery in adults with asthma is practically, nonexistent. The purpose of this feasibility study was to lay groundwork for a larger follow-up clinical trial. OBJECTIVE: To determine whether pulmonary function, asthma symptoms, quality of life, depression, anxiety, and power differ over time in adults with asthma who do and do not practice mental imagery (MI). (Power is the ability to make aware choices with the intention of freely involving oneself in creating desired change.) DESIGN: Randomized controlled study using univariate repeated measures analysis of variance (ANOVA) and replacement through block design. SETTING: Lenox Hill Hospital, an affiliate of New York University Medical School, New York, NY. SUBJECTS: Sixty-eight adults with symptomatic asthma, after 4 weeks of baseline data collection and analysis, met requirements for this randomized controlled study. Thirty-three completed pulmonary function as well as self-report tests at 4 time points over 17 weeks. The 16 experimental participants also completed the 4-session imagery protocol. INTERVENTION: Individual imagery instruction (week 1) and follow-up (weeks 4, 9, 15). Participants were given 7 imagery exercises to select from and practice 3 times a day for a total of 15 minutes. MAIN OUTCOME MEASURES: 1) Spirometry (FEV1); 2) medication use; 3) Asthma Quality of Life Questionnaire; 4) Beck Depression Inventory; 5) Spielberger Anxiety Scales (A-State and A-Trait); 6) Barrett Power as Knowing Participation in Change Tool, Version II; 7) Epstein Balloon Test of Ability to Image. RESULTS: There was little evidence of statistical change in this feasibility study; yet, valuable lessons were learned. Paired t-tests indicated there was a significant difference in the total power scores in the imagery group, and in the expected direction (two-tailed, t-statistic = -2.3, P = 0.035) and the choices sub-scale (two-tailed, tstatistic = -2.93, P = 0.01) of the power instrument from weeks one to 16 of the study. Eight of 17 (47%) participants in the MI group reduced or discontinued their medications. Three of 16 (19%) participants in the control group reduced their medications; none discontinued. Chi-square indicated differences between groups (X2 = 4.66, P = 0.05). Persons who reduced or discontinued their medications showed neither an increase in pulmonary function prior to medication discontinuation, nor a fall in these parameters following discontinuation. CONCLUSIONS: Findings related to major outcome measures must be viewed with caution due to the small sample size resulting from attrition related to labor intensiveness and, therefore, low statistical power. However, the study did provide significant data to plan a larger scale study of the use of mental imagery with adult asthmatics. The study also demonstrated that imagery is inexpensive, safe and, with training, can be used as an adjunct therapy by patients themselves. Its efficacy needs additional exploration. Further research for adults with asthma who practice imagery is important, as current treatments are not entirely efficacious. Lessons learned in this study may facilitate improvement in research designs.

A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation.

Context. Antiepileptic drugs (AEDs) are frequently used for their beneficial mood effects.Objective. We sought to determine if there was a quantifiable effect on mood of the vagus nerve stimulator (VNS) when used as an antiseizure treatment.Design. Mood was assessed before and 3 months after VNS implantation in adult epilepsy patients. A group of adult epilepsy patients on stable AED regimens were used as a comparison group. AED regimens were unchanged during the study. The change in mood scale scores across time was assessed by t test (intragroup) and two-factor repeated-measures ANOVA (intergroup).Setting. An epilepsy center in a university hospital was the setting.Subjects. Twenty consecutive adult epilepsy patients undergoing VNS implantation to improve seizure control and twenty adult seizure patients with no intervention were enrolled.Main outcome measures. The mood scales used were the Cornell Dysthymia Rating Scale (CDRS) and the Hamilton Depression (Ham-D), Hamilton Rating Scale for Anxiety (Ham-A), and Beck Depression Inventory (BDI) scales.Results. The VNS group showed a significant decrease in mood scale scores across time (t test CDRS P = 0.001, Ham-D P = 0.017, BDI P = 0.045), indicating a decrease in depressive symptoms. The Ham-A scores in the VNS group and the comparison group scores did not significantly change across time. There were no significant differences between groups across time, although the BDI approached significance at P = 0.07. The VNS group had a significant decrease in seizure frequency compared with the comparison group (P = 0.01). There was no difference in mood scales over time between the VNS treatment responders (defined by >50% decrease in seizure frequency) and nonresponders, suggesting dissociation between seizure frequency reduction and mood change.Conclusion. VNS treatment is associated with mood improvement as measured by multiple scales, but differences in mood scale scores over time between the VNS and a comparison group were not found.