Day 1 :
National Institute of Neurological Disease and Stroke, USA
Keynote: A novel therapeutic approach to ameliorate the Parkinsion’s and Alzheimer’s Disease phenotypes
Time : 09:30-10:10
Pant received his M.A. and Ph.D. degrees in Physics from Agra University, Agra, India. His postdoctoral studies were conducted on the mechanisms of electron and ion transport in model membrane systems at the Department of Biophysics at Michigan State University. He joined the Laboratory of Neurobiology in the NIMH as a senior staff fellow in 1974 with Dr. Ichiji Tasaki where he studied the function of the axonal cytoskeleton in the squid giant axon. In 1979 he moved to the NIAAA extending his studies on the neuronal cytoskeleton and the effects of alcohol on its regulation. Dr. Pant moved to the NINDS, Laboratory of Neurochemistry in 1987 where he is presently chief of the section on Cytoskeleton Regulation. His laboratory is studying the mechanisms of topographic regulation of neuronal cytoskeleton proteins by post-translational modification, including the role of kinase cascades in normal brain and during neurodegeneration.
The phosphorylation activity is tightly regulated under physiological conditions in the nervous system. Under neuropathological conditions, however, it is deregulated and induces pathology resembling that seen in many neurodegenerative diseases such as Alzheimer’s, (AD), Parkinsion’s (PD) , Amyotrophic Lateral Sclerosis (ALS). During the course of our studies to understand the molecular and cellular basis of the regulation of the cytoskeleton phosphorylation we identified a neuronal cell cycle like kinase , cyclin dependent kinase 5 (Cdk5), together with its activator p35, as a major kinase regulating the topographic neuronal cytoskeleton phosphorylation. However, it is hyperactivated and caused deregulated by neuronal insults (A-beta, glutamate, oxidative stress, mutations and other). Cdk5 is hyperactivated as a stable complex with p25 (a truncated fragment of p35) and induces hyperphosphorylated tau, synuclein and NFPs as seen in AD, PD and ALS. At autopsy, AD, PD and ALS brains display hyperactive Cdk5 (Cdk5/p25) and have confirmed that Cdk5/p25 induces neuroinflammation, tau and NF hyperphorylation along with cell death. A p25-overexpressing (P25Tg) AD model mouse displays the typical AD phenotypes. Accordingly, hyperactive Cdk5/p25 has been identified as a possible therapeutic target for these neurodegenerative diseases. All the therapeutic approaches inhibiting activities of kinases have been by interfering with ATP binding domains of the kinases that turned out to be non-specific and highly toxic. To modulate the Cdk5 activity instead of using the analogs of ATP we decided to study the effect of different truncated fragments of p35 on the regulation of Cdk5 activity. We identified a small peptide p5 (24 aa) bind with Cdk5 with higher affinity than p25 and selectively inhibited Cdk5/ p25 hyperactivity in culture, reduced tau, NFP hyperphosphorylation and cell death without toxicity and affecting endogenous Cdk5/p35 activity. The question arose will p5 be non toxic in vivo, in animals as in cell cultures and may prevent the phenotypes of an AD, PD and ALS transgenic mice models? Consistent with the model, we succeeded in showing that pathological and behavioral phenotypes in PD (MPTP) and AD (P25Tg) model mice can be reduced after treatment with modified p5 (TFP5) . We propose that TFP5 is novel therapeutic candidate to prevent PD and AD phenotypes and pathologies.
Mount Sinai School of Medicine, USA
Keynote: Mechanism of carotid stroke
Time : 10:10-10:50
Jesse Weinberger has completed his MD at the age of 23 years from The Johns Hopkins University School of Medicine, Neurology Residency at The Mount Sinai Hospital and Postdoctoral studies at the University of Pennsylvania School of Medicine. He is a Professor of Neurology and Director of the Neurovascular Laboratory at the Icahn School of Medicine at Mount Sinai. He has published more than 130 papers in reputed journals and has been serving as an editorial board member of repute.
Extra cranial internal carotid stenosis is a significant cause of stroke. However most patients with carotid stenosis remain a symptomatic even with high grade stenosis. Ultrasound studies of plaque morphology have been used to identify vulnerable plaque prone to rupture and embolization. Heterogeneous plaques with lucent areas are associated with a higher incidence of stroke and TIA. These lucencies correlate with thrombus and lipid on pathology. Sequential studies indicate that plaque growth is associated with stroke events. Further studies with black blood MRI document regression and solidification of plaque with state on medication. Ultrasound imaging of carotid plaque morphology provides a useful tool for identifying patients with a symptomatic carotid stenosis who may benefit most from interventional procedures to prevent stroke.
University of Ottawa Canada
Keynote: Timing of Anticoagulant Re-Initiation following Intracerebral Hemorrhage in patients with Mechanical Heart Valves: Meta-Analysis and Survey for Current Practice
Time : 11:10-11:50
Ottawa.rnrnAfter graduating from medical school he completed his neurosurgery training at University of Ottawa in 2010. He also completed two fellowships in complex spine surgery and minimally invasive skull base surgery. Additionally, he has training in clinical epidemiology and biostatistics (MSc, Epidemiology and Biostatistics 2011) and has completed the Clinician Investigator Program certified by the Royall College of Physician and Surgeons of Canada (RCPSC). rnrnDr. AlKherayf’s clinical practice is focused on complex spine surgery, minimally invasive cranial surgery and complex cranio-cervical reconstruction. His clinical research interests lie on translational primary brain tumor research, clinical trials, and spinal cord injury. He has authored and co-authored many research papers and abstracts, and spoken at many international conferences. Dr. AlKherayf has special interest in neurosurgery and spine education by directing many training courses. He also has been serving as an editorial board member of many journals.rn
Background: rnWhile oral anticoagulation (OAC) is universally indicated for patients with mechanical heart valves (MHVs), the time for OAC re-initiation following anticoagulant-associated intracerebral hemorrhage (ICH) is uncertain. We sought to determine the optimal timing for restarting the OAC and the associated clinical outcomes in patients with MHVs following ICH. Furthermore, we surveyed the practice preferences of North American neurosurgeons and thrombosis experts on optimal timing of restarting the OAC in this particular group of patients.rnrnMethodsrnWe performed a systematic review and a meta-analysis of studies published from January 1950 to April 2014. Medline (Ovid), Embase, Scopus, the Cochrane Library, the Cochrane Controlled Trials Register, LILACS, Web of Science and Global Health were searched for studies reporting the time for re-initiation of OAC in patients with MHV following ICH. Extracted data was on the type of initial ICH, use of cranial surgery, presence of atrial fibrillation, type of MHV, position of MHV, number of MHVs, and timing of OAC re-initiation. In addition, the criteria for study selection included data on valve thrombosis, thromboembolic events or ICH recurrence data, calculated absolute risks, and assessing the effect of anticoagulant resumption timing on ICH recurrence via meta-regression.rnA cross-sectional survey was disseminated to North American members of the American Association of Neurological Surgeons and the International Society for Thrombosis and Haemostasis. Demographic factors, as well as a clinical scenario with 14 modifiable clinical risk factors were included in the survey. rnrnResultsrn23 case-series and case-reports were identified and meta-regression was done. Overall proportion of ICH recurrence was 13% (95% confidence interval [CI], 7% – 25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3% - 17%) and 12% (95% CI, 5% - 23%), respectively. A trend towards lower ICH recurrence was observed with delayed OAC re-initiation (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with OAC re-initiation at 3 days to 0% with re-initiation at 16 days.rnrn504 physicians completed our survey (response rate= 34.3%). Majority of participants were affiliated with academic centers, and managed ≤ 10 ICH patients with MHV per year. There was wide distribution in response on optimal timing for OAC re-initiation following an ICH: 59% and 60% preferred to re-start OAC between 3 and 14 days following the hemorrhagic event (median = 6-7 days). Smaller hemorrhages (<30cm2), CHADS2 score ≥2, concomitant venous thromboembolism, mitral valve prosthesis, caged-ball valves and multiple valves prompted earlier OAC re-initiation.rnrnConclusionrnFrom our meta-analysis restarting OAC in day 4 seems to be associated with low risk of recurrent ICH or valve thrombosis, however this conclusion is limited by the quality of the studies. We support the urgent need for high-quality randomized studies in this population.rnrnMoreover, based on our collected survey data, there is a wide variation in the current practice of neurosurgeons and thrombosis specialists when they encounter patients with ICH and MHV, though decisions were influenced by patient- and valve-related factors. As our observed variation likely reflects the immense gap in current evidence, prospective randomized trials in this population are therefore urgently needed.rn
Virginia Tech Carilion School of Medicine, USA
Keynote: Cardioembolic stroke; Sources of embolic material with related distribution, imaging for trans-vascular interventions, and associated embolic complications
Time : 11:50-12:30
Evelyn Garcia completed her M.D. at the University of New Mexico School of Medicine, Diagnostic Radiology residency at the University of New Mexico Medical Center, and Body Imaging fellowship at the University of Utah Medical Center. She is board certified in Diagnostic Radiology and Cardiovascular Computed Tomography. She is the Chairman and Medical Director of Radiology at Virginia Tech Carilion School of Medicine and of Carilion Clinic, a six hospital system with 800 bed flagship Level I Trauma and Stroke certified center. She is imager for the structural heart valve team of Carilion Clinic.
As societies around the world age and lifespans increase, we are challenged by the increasing incidence of cardioembolic stroke and the associated human and resource related impact on society. This has led to the development of transvascular procedures to address disease states in this fragile patient cohort in whom surgery is frequently contraindicated based on comorbidities. Atrial Fibrillation, the leading cause of cardioembolic disease, valvular sources, and cardiac chamber sources with typical end vessel distribution will be discussed. Pre-procedure imaging, identifiable sources of potential embolic complications, and intra-procedure prophylaxis will be presented.
NeuroGen Brain & Spine Institute, India
Time : 12:30-13:10
Alok Sharma is a Neurosurgeon and presently Professor & Head of Department of Neurosurgery at the LTMG Hospital & LTM Medical College and the Director of the NeuroGen Brain & Spine Institute and Consultant Neurosurgeon at the Fortis Hospital in Mumbai, India. He has authored 12 books, edited 2 books, contributed chapters to 8 other books and has 83 scientific publications in medical journals. He has made 146 scientific c presentations all over the world & has conducted several national and international trials and has been conferred with numerous honors and awards in his distinguished career. He has organized many international and national conferences and regularly conducts hands-on training workshops on Micro vascular Surgery, Neuro endoscopy and Spinal fixations. He has been committed to both basic as well as clinical research in attempting to find an answer to the problems of paralysis and neurological deficits that occur following injury and diseases of the nervous system. Is the pioneer of Stem cell therapy in India and has setup the Stem cell and Genetic research laboratory at the LTMG hospital & LTM Medical College. He has also created the NeuroGen Brain and Spine institute which is India’s first dedicated Stem Cell Therapy and Neurorehabilitation Hospital. He has published path breaking results of Stem Cell therapy in Pediatric Neuro developmental disorders such as Autism and Cerebral palsy as well as in other conditions such as Muscular dystrophy and Spinal cord injury. He is the founder of the “Indian Journal of Stem Cell Therapy” and on the editorial board of 4 other journals. He is the Founding President of the “Stem Cell Society of India” and the Vice President of the “International Association of Neurorestoratology”. His other special interests include Revascularization surgery for cerebral ischemia, Psychosurgery, Stereotactic surgery, Neuroendoscopy, Spinal surgery and Neurotrauma.
Stem cell therapy has shown great potential as a treatment strategy for neurological disorders. Autologous bone marrow mononuclear cells have shown a positive outcome in these disorders due to their obtainability, safety and efficacy. In autism, out of 32, 92% cases showed improved social interaction, emotional response, speech and communication, behavior, cognition and sensory aspect on ISAA, CGI and FIM/WeeFIM. In cerebral palsy, 95% out of 40 patients showed improvements in oromotor activities, neck control, sitting balance, standing, walking balance and speech. These improvements correlated with improved brain metabolism recorded in the PET CT scan. In spinal cord injury, 91% out of 110 patients in thoracolumbar SCI and 74% out of 56 patients with cervical SCI showed improvement in spasticity, sensation, trunk control, bladder management, standing and sitting balance, ambulation and ADLs. Changes were recorded in ASIA, FIM scale and electrophysiological studies. In head injury, 93% out of 14 cases showed improvement in balance, voluntary control, muscle tone, memory, oromotor activities, cognition, coordination, speech, communication, ambulation and ADLs. In muscular dystrophy, 86.67% out of 150 showed improved strength in trunk, upper and lower limbs along with gait. 6 patients demonstrated muscle regeneration on musculoskeletal MRI and 9 showed improvement in EMG. In ALS, as compared to the control population (n=20), the survival duration of the treated population (n=37) increased by 30.38 months. In Stroke, improvements were observed in ambulation, hand function and standing and walking balance with ischemic stroke demonstrating better recovery than haemorrhagic stroke. No major adverse events were reported.