Transcranial Infrared Laser Stimulation for the Treatment of Traumatic Brain Injury: A Case Series.

Introduction: This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI). Methods: Eleven participants who were diagnosed with TBI after full neurological examination and MRI evaluation by a board-certified neurologist completed five to eight 20-minute TILS sessions using the Cytonsys CytonPro-5000 apparatus (pilot laser control, focused wavelength of 1064 nm, maximum output power of 10W, maximum optical power density of 500 mW/cm2, effective area 4.5 cm2 in diameter). Per TILS session, participants underwent a laser dose of 250 mW/cm2 continuous laser wave to each hemisphere using predetermined patient-specific coordinates. Structural imaging was used to neuronavigate individual treatment targets in the frontal cortex (Brodmann area 10). The primary safety measure for this study was the occurrence of adverse events (AEs) or serious adverse events (SAEs). The primary efficacy outcome measure was the participant-rated global rating of change (GRC) post-intervention. Secondary outcome measures included a battery of neuropsychological testing and mood questionnaires done both pre- and post-intervention. Results: All patients enrolled in this study protocol were able to tolerate the study procedures without any AEs or SAEs. Nine out of eleven participants had clinically significant improvements in GRC score (≥ +2). Neuropsychological testing and mood questionnaire outcomes also suggested a positive therapeutic effect. Conclusion: This study provides preliminary evidence supporting the safety and potential efficacy of TILS as a non-invasive clinical intervention for individuals with TBI.

Translating state-of-the-art brain magnetic resonance imaging (MRI) techniques into clinical practice: multimodal MRI differentiates dementia subtypes in a traditional clinical setting.

BACKGROUND: This study sought to validate the clinical utility of multimodal magnetic resonance imaging (MRI) techniques in the assessment of neurodegenerative disorders. We intended to demonstrate that advanced neuroimaging techniques commonly used in research can effectively be employed in clinical practice to accurately differentiate heathy aging and dementia subtypes. METHODS: Twenty patients with dementia of the Alzheimer's type (DAT) and 18 patients with Parkinson's disease dementia (PDD) were identified using gold-standard techniques. Twenty-three healthy, age and sex matched control participants were also recruited. All participants underwent multimodal MRI including T1 structural, diffusion tensor imaging (DTI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS). MRI modalities were evaluated by trained neuroimaging readers and were separately assessed using cross-validated, iterative discriminant function analyses with subsequent feature reduction techniques. In this way, each modality was evaluated for its ability to differentiate patients with dementia from healthy controls as well as to differentiate dementia subtypes. RESULTS: Following individual and group feature reduction, each of the multimodal MRI metrics except MRS successfully differentiated healthy aging from dementia and also demonstrated distinct dementia subtypes. Using the following ten metrics, excellent separation (95.5% accuracy, 92.3% sensitivity; 100.0% specificity) was achieved between healthy aging and neurodegenerative conditions: volume of the left frontal pole, left occipital pole, right posterior superior temporal gyrus, left posterior cingulate gyrus, right planum temporale; perfusion of the left hippocampus and left occipital lobe; fractional anisotropy (FA) of the forceps major and bilateral anterior thalamic radiation. Using volume of the left frontal pole, right posterior superior temporal gyrus, left posterior cingulate gyrus, perfusion of the left hippocampus and left occipital lobe; FA of the forceps major and bilateral anterior thalamic radiation, neurodegenerative subtypes were accurately differentiated as well (87.8% accuracy, 95.2% sensitivity; 85.0% specificity). CONCLUSIONS: Regional volumetrics, DTI metrics, and ASL successfully differentiated dementia patients from controls with sufficient sensitivity to differentiate dementia subtypes. Similarly, feature reduction results suggest that advanced analyses can meaningfully identify brain regions with the most positive predictive value and discriminant validity. Together, these advanced neuroimaging techniques can contribute significantly to diagnosis and treatment planning for individual patients.

Treatment of Dementia With Bosutinib: An Open-Label Study of a Tyrosine Kinase Inhibitor.

OBJECTIVE: The pursuit of an effective therapeutic intervention for dementia has inspired interest in the class of medications known as tyrosine kinase inhibitors such as bosutinib. METHODS: Thirty-one patients with probable Alzheimer dementia or Parkinson spectrum disorder with dementia completed 12 months of bosutinib therapy and an additional 12 months of follow-up. The Clinical Dementia Rating scale (as estimated by the Quick Dementia Rating System [QDRS]) was the primary cognitive status outcome measure. Secondary outcome measures included the Repeatable Battery Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment. Cox regression methods were used to compare results with population-based estimates of cognitive decline. RESULTS: The present article reports on cognitive outcomes obtained at 12 months for 31 participants and up to 24 months for a 16-participant subset. Safety and tolerability of bosutinib were confirmed among the study population (Mage = 73.7 years, SDage = 14 years). Bosutinib was associated with less worsening in Clinical Dementia Rating (CDR) scores (hazard ratio = -0.62, p < 0.001, 95% confidence interval [CI]: -1.02 to -0.30) and less decline in RBANS performance (hazard ratio = -3.42, p < 0.001, 95% CI: -3.59 to -3.72) during the year of treatment than population-based estimates of decline. In the 24-month follow-up, wherein 16 patients were observed after 1 year postintervention, 31.2% of participants exhibited worsened CDR levels compared with their 12-month performances. CONCLUSIONS: Results support an overall positive outcome after 1 year of bosutinib. Future studies should explore the relationship between tyrosine kinases and neurodegenerative pathology as well as related avenues of treatment.