Day 1 :
Keynote Forum
Helieh Oz
UK Medical Center, USA
Keynote: Biomarker surrogates for inflammatory and neuropathic complications and pain related hypersensitivity
Time : 9:30AM
Biography:
Dr Helieh Oz has a DVM, MS (U. IL); PhD (U. MN) and clinical translational research certificate (U.KY). Dr Oz is an active member of American Association of Gastroenterology (AGA) and AGA Fellow (AGAF) and associate in Rome Foundation. Dr Oz is Immuno-Microbiologist with expertise in inflammatory/infectious diseases, drugs discovery, pathogenesis, innate/mucosal Immunity, and micronutrient, animal models and pain related behavioural modifications. She has over 90 publications and served as Lead Editor for special issues. Dr Oz serves on different editorial advisory board committees including Center of Excellence for Medical Research and Innovative Products, Walailak University Thailand and is an avid reviewer for several peer-reviewed journals.
Abstract:
Biomarkers are measurable indicators for biological conditions, which extend from normal biological processes, to pathological progress as well as pharmacological response and therapeutical interventions. Biomarker surrogates are required for early diagnosis and treatments of chronic inflammatory and neurological disorders. Appropriate surrogates are required to be sensitive, specific, noninvasive and feasible yet to predict recoveries. Effective biomarkers are often involved in pathophysiological chain. These markers can be classified as simple and nonspecific (e.g. blood pressure, hematogram, BMI), more specific (e.g. enzymes, cytokines, chimokines) or complex and expensive (e.g. FMRI, PET and, CT scans). Pro-inflammatory cytokine, tumor necrosis factor α (TNFα) is released during the early process of inflammatory response following insults. TNFα is a prominent inflammatory biomarker which up-regulates various inflammatory cytokines and chimokines biomarkers, to initiate acute and chronic stages of inflammation and pain related sensation in inflammatory and neurophathic patients and models. TNFα is released by activate macrophages, microglia, neurons, astroglia, CD4+ lymphocytes, and natural killer cells. In a historical clinical trial (1988) subjects were injected with TNFα when shortly after had developed fever, pain and general malaise. As, the initial inflammatory insult primes the immune system, the succeeding insult/s amplify/s deleterious responses for inflammatory and neuropathic disprders. Dysregulation of TNFα contributes to development of inflammatory conditions such as headache, periodontal, temporomandibular and neuropathic pain. Trigeminal neuropathic pain is common following trigeminal nerve damage post surgical procedures and maxillofacial injuries. Analysis of proteomic profiling at multiple time points identify several altered levels of inflammatory cytokines and chimokines. This presentation will explore surrogate markers of inflammatory and neuropathic disorders and their implication in diagnostics as well as possible clinical interventions.
Keynote Forum
Barbara Arrowsmith Young
Arrowsmith Program, Canada
Keynote: A Personal Journey Into the World of the Brain: Shaping the Mind/Function and Plasticity
Time : 10:15AM
Biography:
Barbara Arrowsmith Young holds both a B.A.Sc. in Child Studies from the University of Guelph, and a Master’s degree in School Psychology from the University of Toronto (Ontario Institute for Studies in Education). After her undergraduate studies were completed Barbara worked as the Head Teacher in the lab preschool at the University of Guelph for two years where she began to observe learning differences in preschool children.
Abstract:
In this presentation, Barbara will talk about her journey of discovery, the lines of research she combined and the outcomes achieved over her 35 years as an educator and researcher. She will describe a number of learning disorders, from those that impact the learner in school to those that affect us in life. She will discuss ‘cognitive glitches’ - those areas of weakness that we are all familiar with and often explain away by saying, “I am just not good at navigating, recognizing faces, (fill in the blank).” She will discuss ‘cognitive mismatches’ – situations we find ourselves in where the demand of the task is incompatible with our cognitive functioning and the challenges this presents. Principles of neuroplasticity and the factors leading to both positive and negative brain change will be discussed.
- Neurogenetics | Neurodegenerative Diseases | Neurological Disorders
Location: Conference Hall
Session Introduction
Alina Piekarek
Wrocław University Hospital, Poland
Title: Neurodegeneration in glaucoma- MR Imaging of the brain and the visual pathway changes
Biography:
Alina K. Piekarek has completed her PhD from University of Medical Sciences in Poland and afterwards fellowship at Vienna Medical University, Austria in Department of Biomedical Imaging and Image-guided Therapy. She is European Board Head and Neck Radiologist and leads researches in the neuro-ophthalmology at Wrocław University Hospital, Poland.
Abstract:
This review discusses the glaucomatous degeneration of the brain and the optic pathways detected in MR Imaging. Glaucoma is heterogenous condition causes gradual vision loss associated with the optic pathways damage. The neuropathological mechanisms are not clear. By assessment of the brain using high resolution techniques of magnetic resonance imaging, detailed structural and functional changes can be detected in glaucoma patients. MRI enables the entire visual pathway evaluation, from the optic nerves to the occipital cortex.
Tractography based on diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) can be used to discriminating optic pathway fibers. Diffusion parameters from voxels along of the visual pathway allow to quantitative evaluation of the white matter disintegration. The problem of the crossing fibers, acquisition time, multiparametric analysis, prechiasmatic and postachiasmatic fibers and the spatial resolution artifacts will be discussed by showing examples from my running researches.
High resolution 3D volumetric MR sequences provide the information of cortical glaucomatous reduction, which can be calculate from Brodmann’s areas of the visual cortex. The occipital cortex activity is detected using functional MRI (fMRI) techniques by monocular or biocular stimulation. The certain aspects of fMRI and voxel- based volumetry will be elaborated.The neuro-ophthalmological entities, which can mimic glaucoma will be reviewed and considered based on cases from my Department.Magnetic resonance imaging (MRI) characterizes the glaucomatous neuropathy by detecting the brain changes along the optic pathways.
Laura Hanson
Connect My Brain, USA
Title: The pregnancy relationship and the unborn child: Chronic stress and the epigenetic changes in the brain
Biography:
Dr. Laura Hanson, D.C., MHS, D.I.C.C.P., NDT, is board certified chiropractic pediatric diplomat, neuro-developmental therapist, and has completed her Master’s in Sports Health Science with a concentration in Nutrition. Dr. Hanson has held faculty positions at both Palmer College and Life University from 2003 until 2012. Dr. Hanson is recognized domestically and internationally through her personal teachings to health care professionals, teachers, and parents on the progression of pediatric development.
Dr. Hanson has practice since 1996 in the area of pediatric development and brain based patient management. Dr. Hanson is recognized as a world expert in teaching and caring for children with developmental delay. Her goal is to educate communities on the effects of stress on the developing brain, in ability to conceive a baby, meltdowns and parenting, and chronic ill health.
Abstract:
Statement of the problem: Stress initiates a 3 step reaction: 1) The alarm; 2) resistance; 3) exhaustion. If the third step continues, there is higher risk of long term damage affecting the endocrine glands perpetuating immune exhaustion resulting in functional deterioration. Chronic stress during pregnancy has been found to have a long-lasting effect on the developing offspring into their adult years.
The stress mechanism increases hypothalamic-pituitary-adrenal (HPA) axis output which may cause a loss of placental barrier influencing the fetal physiology changing the regulation of the fetal HPA-axis. A second mechanism is the maternal HPA-axis hormone stimulating the placenta to produce corticotrophin-releasing hormone (CRH) that will enter into the fetal circulation. CRH is a marker determining the length of gestation. Increased levels of HPA-axis hormones could possibly affect the developing child’s nervous system, primarily, the brain glucocorticoid receptor (GR) development. The GR is expressed in almost every cell and regulates genes that control development, metabolism, and immune reaction. A third mechanism is decreased blood flow to the uterus as a result of increased levels of cortisol and catecholamines in the maternal circulation.
According to the HPA axis theory and evidence, stress during pregnancy and during sensitive periods of development can have long-standing changes in the fetus neurodevelopment and behavior. According to Godfrey and Baker, sensitive windows are periods when stress hormones “may alter the development of specific fetal tissues during sensitive periods of development or may lead to long-lasting changes in hormone secretion or tissue hormone sensitivity”.
Patterns of prenatal stress increase maternal cortisol and may cause a considerable increase in fetal cortisol. Maternal anxiety and stress may be associated with complications in pregnancy and may alter programming of the fetal neuroendocrine system.
Ioanna A. Armata
Dr.Georges L-Dumont University Hospital Center and University of Moncton, Canada
Title: Micropeptides translated from polymorphic upstream open reading frames; lessons from Dopa-Responsive Dystonia
Biography:
Dr. Armata is a molecular and cellular neuroscientist, who specializes in dystonia syndromes and myotonic dystrophy 1. Her training and expertise is in the fields of gene expression, functional non-coding mutations, assay development for drug high throughput screenings, and the CRISPR/Cas9 system. She has published over 10 peer reviewed papers, four of which are related to the role of upstream open reading frames in neurological diseases. She obtained her Ph.D. in Neuroscience at Mount Sinai School of Medicine (2008), followed by a postdoctoral fellowship (2008-2012) at Massachusetts General Hospital and Harvard Medical School, and a Research Faculty I appointment at Florida State University (2013-2016), until relocating to Canada for family reasons. At present, she is a Research Fellow holding a joint appointment at Dr. Georges-L.-Dumont University Hospital Centre and the University of Moncton, Canada, studying translational therapeutics for dystonia and myotonic dystrophy 1.
Abstract:
Approximately 50% of human transcripts harbor potential upstream translation start sites (uATGs) that initiate short open reading frames (uORFs) in the five untranslated region (5’ UTR) (Fig. 1A). Translation initiation at a uATG blocks a fraction of ribosomes from reaching the coding ATG (cATG) at the begging of the coding sequence (CDS). Thus, uATG-mediated repression ensures that cATG-protein expression is maintained at optimal levels. Interestingly, some uORFs encode short bioactive proteins with roles different than the role of the CDS-encoded protein. Single nucleotide polymorphisms (SNPs) that “introduce” uATGs in genes that are normally devoid of uATGs, repress CDS translation below optimal levels. About 17 different diseases are linked with SNP-introduced uATGs, among which a single neurological syndrome identified by our work. In particular, carriers of a GCH1 +142C>T SNP manifest Dopa-Responsive Dystonia (DRD), a neurological movement disorder of childhood onset. The GCH1 gene encodes GTP cyclohydrolase 1, a critical enzyme for dopamine (DA) biosynthesis. The +142C>T SNP introduces a uATG/uORF that initiates translation upstream of the GCH1 CDS, diminishing GCH1 protein levels and disrupting DA biosynthesis (Fig. 1B). Furthermore, the introduced uORF translates a 73aa-peptide that accumulates in the nucleus of cultured cells, - in contrast to the cytoplasmic GCH1 -, triggering cellular death. Cases of DRD caused by coding GCH1 mutations are successfully treated with L-Dopa, which compensates for reduced DA levels. Assuming 73aa-triggered death of the dopaminergic-neurons within the brain of 142T patients, L-dopa might be insufficient for these patients, and dystonia could progressively manifest to Parkinson’s Disease. Noteworthy, while translation of micropeptides from physiological uATGs/uORFs has been well demonstrated, only three studies have examined translation of microproteins from SNP-introduced uATGs/uORFs, and only the present study examined their impact on cellular homeostasis. Overall, our findings highlight the biological relevance of micropeptides translated from SNP introduced uATGs/uORFs.
- Clinical Neuroimmunology | Autoimmune Disorders | Neuroinflammation
Location: Conference Hall
Session Introduction
Sebastien Talbot
Université de Montréal, Canada
Title: The context-dependence of Neuro-Immune interplay
Biography:
Dr. Sebastien Talbot laboratory is at the inter-phase of neuroscience and immunology, a novel and highly dynamic field, and combines techniques of molecular and cell biology, optogenetics, tissue clearance and imaging, electrophysiology, neuroanatomy, behavior, and genetics. I aim at identifying the mechanisms and molecules that regulate the interplay between the immune and sensory nervous systems in physiology and pathology. Ultimately, I aim at defining a framework of the neuro-immune interplay at the system level, to decipher how and which sub-population of sensory neurons controls innate and adaptive responses, and to develop new targeted therapies for resolution of chronic inflammatory diseases
Abstract:
The sensory nervous and immune systems, historically considered autonomous, actually work in concert to promote host defense and tissue homeostasis. These systems interact with each other through a common language of cell surface G protein coupled receptors and receptor tyrosine kinases as well as cytokines, growth factors, and neuropeptides. While this bidirectional communication is adaptive in many settings, helping protect from danger, it can also become maladaptive and contribute to disease pathophysiology. The fundamental logic of how, where, and when sensory neurons and immune cells contribute to either health or disease remains, however, unclear. Our lab and others have begun to explore how this neuro-immune reciprocal dialog contributes to physiological and pathological immune responses and sensory disorders. The cumulative results collected so far indicate that there is an important role for nociceptors (noxious stimulus detecting sensory neurons) in driving immune responses, but that this is highly context dependent. To illustrate this concept, our findings in a model of airway inflammation, in which nociceptors seem to have major involvement in type 2 but not type 1 adaptive immunity.
Steven Osterhout
Vitality Healthcare, USA
Title: Bridging the duality of conventional treatment approaches in auto-immunity with environment and lifestyle interventions
Biography:
Dr. Steven Osterhout attained his Pre-Med degree from Western Michigan University, going on to earn his Doctorate of Chiropractic, as well as a post-doctoral Board Certification in Clinical Nutrition. He is a member of the Academy of Anti-Aging Medicine and Academy of Environmental Medicine.
At the young age of twelve, Dr. Osterhout was diagnosed with Type 1 Diabetes. At twenty, he underwent open-heart surgery. Experiencing these two profound health challenges early in life created in him an overwhelming need to find answers to why we get sick.
His personal experience with medicine created a respect for what it can do, but it also gave him an understanding of the expansive room for growth needed to accomplish true health. This led to over twenty years of research, science, and participation in healing strategies from around the world. Integrating these approaches has led to the creation of Vitality Healthcare a medical and natural healing center.
Abstract:
Implementing integrative approaches in auto-immune conditions creates best possible patient outcomes. Modifiable lifestyle choices and navigating environmental triggers reduces inflammatory burdens while soothing a hyper-confused immune response. Redundant, constant immune triggers activating NF-kB expression overwhelms an already self-critical immune response. Cycling specific nutrition, avoiding environmental triggers, directing lifestyle changes, balancing gut microbiome, and retraining immune behavior reduces the NF-kB signaling pathway. Identifying, detoxifying, and healing underlying triggers creates an opportunity for stifling the autoimmune process. This decreases symptoms and generates patient confidence. While inflammation may or may not cause the disease, it is a significant contributor to the pathogenesis of auto-immune expression and neuropathologies like multiple sclerosis. Using these principles as a base approach, along with lifestyle interventions as a platform to minimize inappropriate immune responses, allows medication to be employed at potentially reduced dosages and increased effectiveness. Ultimately patient long-term positive health is leveraged while allowing research to investigate increasingly effective therapies and ultimately an auto-immune solution.
- Neurology | Functional Neurology | Novel Therapeutics
Location: Conference Hall
Session Introduction
Kat Toups
Bay Area Wellness – Functional Medicine Psychiatry and Dementia, USA
Title: Dementia Demystified: A Functional Medicine Approach to Reversing Cognitive Decline and Dementia
Biography:
Kat Toups, MD is a Functional Medicine Psychiatrist who specializes in reversing Mild Cognitive Impairment and Dementia using a Functional Medicine approach. She also uses Functional Medicine in the treatment of Psychiatric, Immune, and brain-based disorders.
Dr. Toups is a Distinguished Fellow of the American Psychiatric Association and a Certified Practitioner by the Institute for Functional Medicine. Dr. Toups was formerly an Assistant Professor at U.C. Davis, where she was the Inpatient Residency Training Director, and later the founded and directed the Bay Area Research Institute, a Clinical Trials Research Center in Lafayette, CA for 12 years. After serving as the Principal Investigator on more than 100 clinical trials for 12 years, including 20 failed trials for Alzheimer's medications, she realized that the elusive cure for Brain and Psychiatric illness was not going to be found in a pill.
Dr. Toups is the author of the upcoming book, Dementia Demystified.
Abstract:
Alzheimer's Disease is a neurodegenerative disorder – but it is not a mysterious, untreatable brain disorder. It is a reversible multisystem illness that occurs due to toxins and Infections and inflammation and lack of hormones and other diet and lifestyle factors. It has a strong auto-immune component as well. Neurodegeneration does not just happen. It happens for reasons, and when we can look at the big picture and address all of the driving factors, we can gain traction in stopping and reversing the degenerative process. Alzheimer's Dementia is a multi-factorial disease, and it is rarely due to just one thing. In order to reverse dementia, we have to look at, and rectify, all of the factors that contribute: Metabolic, nutritional, toxic, inflammatory, infectious, autoimmune, and/or withdrawal of trophic support (like hormones and nutrients). Once we can remove and rebalance the underlying causes of neurodegeneration, we can call upon Neuroplasticity and Neuro-regeneration – the amazing mechanisms our brains have to restore themselves.Dr. Toups will discuss the Functional Medicine approach she used to reverse her own dementia and how to evaluate patients with Mild Cognitive Impairment and Dementia using a Functional approach to determine the root causes of their illness.
Herbert Alejandro Manosalva
University of Toronto and Sunnybrook Hospital, Canada
Title: Double hit theory for the development of Vascular Parkinsonism
Biography:
Herbert Alejandro Manosalva has completed his medical and neurology degree at the National University of Colombia. He worked in the Netherlands Antilles for 8 years, and due to his passion for neurosciences he moved to Canada, where he completed his Fellowship in Movement Disorders & Medical Genetics applied to the field of movement disorders and neurology at the University of Alberta. Due to his research interest in Vascular Parkinsonism he published a study in a novel form of screening patients with this condition in the Stroke prevention clinic. He completed at the same university his second Fellowship in cerebrovascular diseases, before he moved to the University of Toronto in Ontario at the Sunnybrook Hospital. He is currently planning a study for patients with central retinal artery occlusion, condition that has no current effective treatment.
Abstract:
One decoding the components of the network involved in the genesis of Vascular Parkinsonism (VasP) in a Tertiary Care Stroke Prevention Clinic (SPC). After screening for potential patients with VasP (using the Tanner Questionnaire and the FMAS score1) during 12 consecutive months in a SPC (240 candidates) we found 46 patients with potential Parkinsonism (TQ>4). Patients were examined clinically to detect a hypokinetic rigid syndrome, and the FMAS score was used to find candidates with VasP (8/46). The location of the lesions was studied in the two groups using the neuroimaging tests (CT scan and/or Brain MRI) and its pattern. The anatomical networks for this syndrome has been suggested in different studies mainly affecting the basal ganglia structures, thalamus and frontal lobes.
Two frequent patterns were found: one with basal ganglia lesions and frontal lobe lesions, and the other one involving the thalamus and frontal lobes. But only the pattern involving the Lenticular nucleus (BG) and frontal lobes was significantly associated to the group of VasP (X2 Fisher exact test p<0.0005 Odds ratio CI 95% (9.6-108)); whereas the pattern thalamus – frontal lobes was not significantly different between the two groups (X2 Fisher exact test p=0.828 Odds ratio CI 95% (0.5-2.8)) Table 1.
In conclusion patients with double lesion pattern located at the BG (Lenticular nucleus) and frontal lobes were found to have VasP. A two strategic location hit is presumed to be required to develop this condition. What neurotransmitters and neuro immunological changes may occur in this network that could explain the onset of Parkinsonism may require further investigation. It is presumed that changes in Dopamine neuro receptors and neuro immunomodulatory molecules may play a role in its pathogenesis. Further studies would be required in the future to confirm these findings.