11^th World Congress on Neurology and Therapeutics March 27-29, 2017 Madrid, Spain

Biography:

Harish C Pant received his MA and PhD 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. He moved to the NINDS, Laboratory of Neurochemistry in 1987 where he is presently Chief of the Section on Cytoskeleton Regulation. His laboratory is working on 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.

Abstract:

The biology of neurodegeneration program evolved from our laboratory studying the basic biology of neuronal cytoskeletal protein phosphorylation during development and normal function in the adult. To understand the molecular basis of neurodegeneration our major focus has been to study the regulation of compartment-specific patterns of cytoskeletal protein phosphorylation in neuronal perikarya and axons. We have demonstrated that phosphorylation of the numerous acceptor sites on such proteins as Tau and neurofilament are tightly and topographically regulated and generally confined to the axonal compartment under physiological conditions. However, during neuronal insults, it is deregulated induces neuropathology. During our course of studies to understand the biology of this regulation we identified cyclin dependent kinase5 (Cdk5); a neuron specific kinase involved in the nervous system development, function and survival. It was recognized that in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s (PD) and Amyotrophic lateral sclerosis (ALS) the pathology was characterized by aberrant and hyper activation of Cdk5 and accumulation of aberrantly hyper phosphorylated cytoskeletal proteins in cell bodies, suggesting that topographic regulation had been compromised. This led inevitably into studies of neurodegeneration in cell culture and model mice with emphasis on Cdk5, that targets numerous neuronal proteins including cytoskeletal protein regulation by phosphorylation, which when deregulated, is responsible for the pathology seen in neurodegenerative diseases. In cell systems, neuronal stress leads to deregulated kinases. Recently we have discovered peptides derived from, p35, and a neuron specific activator of Cdk5, which rescue cells in vitro from stress induced pathology. The questions currently being investigated are (1) how is cytoskeletal protein phosphorylation topographically regulated in neurons? (2) What factors are responsible for the deregulation of Cdk5 in neurons? (3) Can mouse models of AD, PD and ALS be treated therapeutically with peptides that inhibit deregulated Cdk5?

Biography:

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 certifi ed 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 fl agship Level I Trauma and Stroke certifi ed center. She is imager for the structural heart valve team of Carilion Clinic.

Abstract:

Point: Successful development of comprehensive stroke service is possible in the rural setting.

The Issue: Stroke is the 4th leading cause of death in the Unites States and 2nd leading cause of death in the EU and Europe. Total ischemic lesion volume of 1.5-4.3 cm3 equates to the death of approximately 2 million neurons and the decoupling of 1 billion synapses. Unique geography in the US leads to large areas of spars population and limitation of service availability. We have created a comprehensive stroke program through the collaboration of multiple subspecialists including interventional neuroradiologists, neurologists, diagnostic radiologists, emergency physicians and first responders. These services are supported and coordinated through a unique logistics command center staffed 24 hours a day, 365 days a year with highly specialized nurses and emergency medicine technicians. Each patient’s journey begins with a contact to this center followed by an elegantly choreographed journey from transport through treatment and recovery.

The Geography: Roanoke Virginia is a small city in Appalachian Western Virginia with a population of 100,000 and catchment area of approximately 350,000. It is geographically isolated from large urban areas. Sites with equivalent capabilities are located 121 miles Northeast, University of Virginia Medical Center, 127 miles Southeast, Duke Medical Center, and 106 miles Southwest, Wake Forest Baptist Medical Center. Because time to treatment is critical, time being neurons, the success of this model represents hope for populations in similar regions.

The Message: Rural locations with geographical separation do not preclude development and growth of successful high quality stroke center programs. It is feasible to provide these services to rural regions with interdisciplinary collaboration, specialized communication and efficient transportation.

Biography:

Anthony E Kline, PhD, is a Professor in the Departments of Physical Medicine and Rehabilitation, Critical Care Medicine, and the Safar Center for Resuscitation Research at the University of Pittsburgh. His research includes neurobehavioral recovery and learning after Traumatic Brain Injury (TBI). Therapeutic strategies that include pharma­cotherapy and environmental enrichment are utilized alone or in combination in an attempt to restore function and/or attenuate TBI-induced deficits. Another interest is the evaluation of pharmacological agents that may alter TBI and to elucidate potential mechanisms for the observed effects.

Abstract:

Introduction: Traumatic Brain Injury (TBI) affects two million people in the United States each year and several million more worldwide, making it a significant health care issue. Motor vehicle accidents and falls resulting in a blow to the head are the typical causes of TBI in the general population, whereas blasts and shrapnel from improvised explosive devices are the leading causes for military personnel in active war zones. Brain traumas range from mild to severe with the former being the case in the majority of occurrences and generally not displaying marked behavioral symptoms, while the latter occurs less often, but presents significant motor and/or cognitive dysfunction, as well as agitation and aggression. Numerous preclinical therapies have been evaluated, but have not translated to the clinic.

Methods: In this presentation, two therapeutic interventions that are used in my laboratory will be discussed. The first is Environmental Enrichment (EE), a preclinical model of neurorehabilitation that has been shown to confer motor, cognitive, and histological benefits after TBI. The second is the use of Antipsychotic Drugs (APDs). Because agitation is common after TBI, patients are provided APDs so that they can be safely managed. The use of chronic as well as intermittent APD administration will be discussed, as well as their combination with EE. The data presented are derived from anesthetized adult male/female rats that received a cortical impact of moderate severity or sham injury and were then randomly assigned to EE or standard (STD) housing.

Results: The results generally show that motor and cognitive function is significantly improved in the EE vs. vehicle control groups and that APDs impede functional recovery.

Conclusions: EE can be considered a robust preclinical model of neurorehabilitation. Moreover, the use of APDs, especially haloperidol and risperidone after TBI should be used sparingly to reduce compromising recovery and/or attenuating the efficacy of neurorehabilitation.

Biography:

Jyri Kuusela is the founder of NeuroVitalia and Ataman Science. He is also Neurofeedback lecturer of EEG Info-Europe and qEEG/ERP lecturer of HBImed.

Abstract:

Electroencephalographic (EEG) biofeedback or often referred as Neurofeedback (NFB) was discovered about 40 years ago. Over a long period, the technique remained unpopular, which is investigated by few enthusiasts. In the late 90s and in early 2000s, there started a new era of the Neurofeedback. The technological advances helped faster development and quicker testing of new protocols and methods. During the last years, close to 200 publications are made every year about NFB and thousands of clinicians are applying the technique in daily basis in their practices. One of the most investigated topics has been ADD/ ADHD and in 2012, American Academy of Pediatrics placed EEG biofeedback as a level-1 “Best Supported” intervention to ADHD. The Institute of Social Research and Development of Uncommon Diseases together with NeuroVitalia is treating patients with NFB in Clinical Hospital San Carlos. We apply the technique to wide variety of patients. We treat, for example, tics, Tourette’s syndrome, and epilepsy, where NFB is known to provide help, but we have also started applying it to patients with leucodystrophy, neuromuscular diseases and brain injuries. In the clinics of NeuroVitalia, we usually treat ADHD, autism, migraine, anxiety and depression. We also have many peak performance clients.

Biography:

Corina Bondi, PhD, is an Assistant Professor in the Department of Physical Medicine and Rehabilitation and at the Safar Center for Resuscitation Research at the University of Pittsburgh. Her research interests focus on characterizing therapeutic strategies after experimental traumatic brain injury, such as pharmacotherapies and environmental enrichment, for complex cognitive processing deficits and distinct neurobehavioral and neurochemical alterations relevant to psychiatric disorders.

Abstract:

Traumatic brain injury (TBI) affects 2 million individuals in the United States each year, and many survivors endure cognitive impairments, while also being vulnerable to neuropsychiatric disorders. Clinical and preclinical research has highlighted the importance of chronic stress as a major risk factor for many psychopathological conditions. In the current study, we are assessing clinically-relevant cognitive-behavioral and anxiety-like dimensions sensitive to both TBI and chronic unpredictable stress (CUS). We hypothesized that moderate TBI produced by controlled cortical impact (CCI) injury, as well as CUS exposure will render cognitive impairments in male rats in an attentional set-shifting test (AST), reduced sucrose preference and open field exploration, blunted weight gain, elevated stress hormones and inflammatory markers. Anesthetized adult male rats were subjected to a CCI (2.8 mm cortical tissue deformation) or sham injury over the right parietal cortex. Rats were then randomly assigned to receive CUS (21 days) or 30 sec of handling (CTRL). Upon cessation of stress, rats were tested for perceived state of anxiety (open field test) and anhedonia (preference of 1% sucrose-water versus regular water). At 4 weeks post-surgery, rats were then tested on the AST, which involves a series of increasingly difficult discriminative tasks to obtain food reward. While TBI and CUS alone impaired behavioral flexibility on AST, as expected, the combination group (TBI+CUS) does not seem to negatively impact exploration in the open field, sucrose preference or AST performance (n=8-12/group). Moreover, serum levels of corticosterone (CORT), and inflammatory markers (IL- 1β and TNFα) were paradoxically reduced in the TBI+CUS rats compared to controls, suggesting a putative enhanced resilience in this group. This ongoing project will provide novel outcomes pertaining to cognitive capability, as well as anxiety- and depressive-like symptoms following overlapping chronic stress exposure and the recovery phase of TBI.

Biography:

David E Vance is a Psychologist at the University of Alabama at Birmingham and is studying Cognitive Remediation and Aging with HIV. He has +180 peer-reviewed publications. He received a White House invitation to attend the first forum on aging with HIV and has participated as an invited member of the USA National Institutes of Health Think Tank – Working Group on HIV and Aging. Recently, he was awarded a 2.8 million dollar grant from the USA National Institute of Mental Health titled, “An RCT of speed of processing training in middle-aged and older adults with HIV.

Abstract:

Between 52-59% of adults with HIV experience HIV-Associated Neurocognitive Disorder (HAND), and both the frequency and severity of such disorders may increase with advancing age. Unfortunately, few pharmacological or behavioral interventions have been shown to be effective. This presentation reviews the overall rationale and development of speed of processing training, a computerized cognitive training program, to improve this specific cognitive ability as well as everyday functioning and quality of life in adults aging with HIV. Although this protocol has been shown to improve speed of processing, everyday functioning, and quality of life in normal, community-dwelling older adults in the Advanced Cognitive Training In Vital Elderly (ACTIVE) study, its efficacy in adults aging with HIV has not been established. Based on our prior work, this current study consists of a pre-post two-year longitudinal experimental design whereby 264 adults with HAND are randomly assigned to one of three training conditions: 1) 10 hours of laboratory-based Speed of Processing Training, 2) 20 hours of laboratory-based Speed of Processing Training, or 3) 10 hours of a standardized computer-contact control (sham) condition. Thus, the description of this randomized, longitudinal clinical trial covers the following: 1) rationale for speed of processing training in those with aging with HIV; 2) overview of overall study design; 3) inclusion/exclusion criteria and diagnosing HAND; 4) cognitive/functional assessment battery; and 5) examination of biomarkers (e.g., IL-6, BDNF). In conclusion, related cognitive interventions are suggested as they may utilize similar features of this current RCT protocol to examine their efficacy.

Biography:

Isabel Lastres-Becker is Associate Professor at the Autonomous University of Madrid, Spain. Her main focus is to uncover the molecular basis of neurodegenerative disorders like Parkinson and Alzheimer’s disease, to try to find a therapeutic target to develop a cure

Abstract:

This preclinical study was aimed at determining if pharmacological targeting of transcription factor NRF2 might provide a disease modifying therapy in the animal model of Parkinson’s disease (PD) that best reproduces the main hallmark of this pathology, i.e. α-synucleinopathy, and associated events including nigral dopaminergic cell death, oxidative stress and neuroinflammation. Pharmacological activation of NRF2 was at the basal ganglia by repurposing dimethyl fumarate (DMF), a drug already in use for the treatment of multiple sclerosis, leading to up-regulation of a battery of cytoprotective genes. Daily oral gavage of DMF protected nigral dopaminergic neurons against α-SYN toxicity and decreased astrocytosis and microgliosis after 1, 3 and 8 weeks from stereotaxic delivery to the ventral midbrain of recombinant adeno-associated viral vector expressing human α-synuclein. This protective effect was not observed in Nrf2-knockout mice. In vitro studies indicated that this neuroprotective effect was correlated with altered regulation of autophagy markers p62, LC3 and LAMP2 in MN9D, BV2 and IMA 2.1 and with a shift in microglial dynamics towards a less pro-inflammatory and more wound-healing phenotype. In postmortem samples of PD patients, the cytoprotective proteins associated with NRF2 expression, NQO1 and SQSTM1/p62, were partly sequestered in Lewy bodies, suggesting impaired neuroprotective capacity of the NRF2 signature. These experiments provide a compelling rationale for targeting NRF2 with DMF as a therapeutic strategy to reinforce endogenous brain defense mechanisms against PD-associated synucleinopathy.

Biography:

Irene Sanchez-Vera completed her PhD in Neuropharmacology from Carlos Haya University Hospital (Malaga, Spain) and has been working as a Postdoctoral Researcher at Carlos Haya University Hospital (Malaga, Spain), Principe Felipe Research Centre (Valencia, Spain), Andalusian Centre of Molecular Biology and Regenerative Medicine (CABIMER, Seville, Spain), Institute de la Vision (Paris, France), University of Valencia (Spain), and Genetic Medicine Institute (Newcastle upon Tyne, UK). Nowadays, she is a Medical Scientific Liaison at Novartis Farmaceutica (Spain). She has publications in reputed international journals in Neuroscience field, and has been serving as Invited Referee in international journals

Abstract:

Introduction: Once-daily Fingolimod (Gilenya®, Novartis Pharma AG) is a sphingosine 1-phosphate receptor modulator approved for relapsing MS treatment. Continuous collection and analysis of real world effectiveness and safety data is the key to making accurate treatment decisions. The objective is to describe basal characteristics and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) followed for ≥12 months in routine clinical practice in Spain.

Methods: Fingoview is a multivariate pool analysis of two observational, retrospective chart reviews, multicenter studies MS Second Line Gate and MS Next, conducted in specialized MS centers in Spain, between November 2014 and December 2015. Pool analysis was prospectively planned. Both studies included patients of both sexes, ≥18 years, diagnosed with RRMS, treated with fingolimod according to SmPC and followed up for ≥12 months after treatment initiation.

Results: Fingoview included 988 patients (70 naïve, 252 post-natalizumab, 666 post first-line injectable DMTs), 68.9% female, mean (SD) age: 40.44 (9.1) years. After 1, 2, 3 years of treatment, mean annual relapse rate decreased by 76.5% (mean: 1.19 to 0.28), 82.4% (0.21) and 86.3% (0.16) compared to the year prior to fingolimod (all p<0.0001). At 12 months, 89.6% of patients had stable or improved EDSS which was maintained in 84.4% of patients at 24 months. New/enlarged T2 lesions, gadolinium-enhancing lesions on T1 or radiologically disease free will be discussed.

Conclusion: After switching to fingolimod, RRMS had significantly suppressed clinical disease activity and most of the patients have a stable EDSS after one year of treatment.

Biography:

Vahe Poghosyan completed his MSc in Mathematics from Yerevan State University and PhD in Neurophysiology from National Academy of Sciences of Armenia. He held positions of Research Scientist in RIKEN Brain Science Institute in Japan, Senior Scientist and Director of Research Training Program at AAI Scientific Cultural Services Ltd. in Cyprus. Currently, he is the Head of MEG Laboratory and Consultant of Neuronavigation at King Fahad Medical City in Riyadh, KSA. He has published more than 20 research papers in high-impact journals in the field of Neuroscience.

Abstract:

Functional localization of eloquent cortices, covering or adjoining the pathological brain regions, is needed during many neurosurgical interventions. In particular, the hemispheric lateralization of language and memory functions as well as localization of cortical regions involved in language processing are often essential, especially in cases of epilepsy surgery. Currently, such localization is performed predominantly through invasive methods: The Wada test (intracarotid sodium amobarbital procedure) is most commonly used to assess the hemispheric dominance of language and memory during the pre-surgical evaluation of patients and, electrocortical stimulation is routinely used intra- or extra-operatively to localize cortical regions underlying receptive and expressive language processing. Although both of these procedures are well-established means for the functional evaluation of eloquent cortex, they have also some important limitations, such as risk of morbidity due to their invasive nature, variability in responses to barbiturate agents and arterial anatomy, limited spatial extent of electrocortical stimulation, which is confined to small area of craniotomy, etc. Magnetoencephalography (MEG) is the most novel, completely non-invasive functional neuroimaging technique capable of generating activation maps for the entire brain in real-time. The evidence from research suggests that MEG can be used effectively to assess the hemispheric dominance of language and memory, and to map the cortical regions supporting the linguistic functions of speech production (Broca’s area) and comprehension (Wernicke's area), in individual patients. Non-invasive mapping of language-specific cortical zones, during routine pre-surgical evaluation of patients, can significantly facilitate surgical planning and reduce morbidity associated with resection of eloquent cortex. In this presentation, I will describe recently developed activation protocols and methodologies for identifying the hemispheric lateralization of language and memory, and mapping of the language-related eloquent cortex. I will highlight the potential of MEG in the pre-surgical evaluation, and will argue for widening the scope of MEG applications in clinical practice.

Biography:

Lahbib Soualmi is an expert in Image Guided Neurosurgical Navigation. He has been, from 1998 until 2008, Director of Neuronavigation Unit, in Montreal Neurological Institute and Hospital, McGill University Health Center (MUHC) and Assistant Professor in the Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. He holds an MS and a PhD in Biomedical Engineering from Ecole Polytechnique of Montreal. In 2008, he relocated to the National Neuroscience Institute at King Fahad Medical City in Riyadh, Saudi Arabia, where he is currently, Consultant of Image Guided Neurosurical Navigation and the Head of Neuronavigation Unit and Intraoperative Surgical Imaging. Furthermore, he has been a Consultant Faculty in the Biomedical Technology Department, King Saud University, Riyadh, Saudi Arabia from 2008 to 2013.

Abstract:

Neurological surgery has always been a highly technological profession. Neuronavigation is this surgical technology that continues to transform neurosurgical interventions into safer and less-invasive procedures. Among other medical technologies, neuronavigation has pushed the limits of conventional neurosurgery, helping in re-defining new and more precise approaches. Its power lies in the ability to virtually combine imaging data to extract comprehensive information that is used to strategize and guide the neurosurgical interventions. What was once a simple localization tool is today a surgical reality tool and an essential piece of technology in the operating theaters (OT). It is used as an information center for providing surgical crew with the right information when it is needed the most. During the surgery, an interactive real-time display can demonstrate the otherwise hidden information that has been generated from multi-modal volumetric images. The information defined during the preoperative plan of the surgical approach can be deployed in the surgical field, enabling selection of the appropriate scalp incision, minimizing the extent of the craniotomy, and thus decreasing considerably the potential risks to the patient. Also during surgery, the navigation accuracy decreases because of the brainshift and tissue removal. The use of intraoperative imaging will redress for these inaccuracies by refreshing the imaging data used by the neuronavigation. Furthermore, intraoperative imaging is allowing the assessment of surgery's objectives (i.e. amount of tumor removal), within the OT itself, while the patient still on the surgical table and before skin closure. Understanding the association between anatomy and imaging for surgical purposes remains a challenge and neuronavigation, when appropriately used, can bridge the gap between them and assist in performing surgery more dexterously and safely. Available new technologies bring a promise of a better and safer tomorrow for neurosurgical interventions. Having these great technological tools should indeed help us in delivering great care

Biography:

Elamir Elsherif is a Neurophysiologist Physician. He has completed his MD from Ain Shams University in Cairo. He did his training in Neurophysiology in Kings County Hospital in Brooklyn, New York. He completed the American Board of Neurophysiologic Monitoring program in Chicago. Currently, he is a Consultant of Intra-operative Neuro-monitoring and the Director of Neurosonology Lab at King Fahd Medical City. He is interested in Cortical Mapping, Neuromodulation and Brain Computer Interfaces.

Abstract:

Intraoperative Neurophysiologic Monitoring (IONM) has been a very dynamic and evolving field in the last few decades, surgeries that were considered inoperable before, due to its consequences of neurological deficits, become more operable. Subtle and safe excision of many brain and spinal cord tumors became routine due to multiple advances including intraoperative neurophysiological monitoring and mapping. Surgeons’ decisions become more enlightened and informed due to multimodalities that give a complete set of information about the function of the sensory, motor and even the autonomic nervous system during surgery. Vigorous wake up test during scoliosis became almost obsolete due to IONM, clipping versus coiling, shunting versus non-shunting and many other neurovascular intraoperative decisions become more informed due to the presence of that amount of information from IONM. Functional mapping can be done pre and intra operative as well, giving more confidence to surgeon with every scalpel move that he is working on the right direction, ensuring safety and integrity of the neural tracts and functions under monitoring. The future of integrating more modalities is unfolding rapidly; integrating Transcranial Doppler with EEG, SSEPs and even functional reserve testing is being developed, giving clearer picture of the dynamic changes in neurovasculature in addition to the electrophysiological changes. The development of dry electrodes and caps can give the neurophysiologist enormous channels and contacts with brain in a shorter and more efficient time during surgeries. The future of neurophysiology can change and change the future of humanity with advancing in Brain Computer Interfaces (BCIs), where the boundaries between neural cells and computer circuits slowly disappear.

Biography:

Sajjad Ali completed his training in Clinical Neurophysiology from the West Midlands Denary, UK and then worked as a Physician Consultant at the Queen Elizabeth Hospital Birmingham (QEHB), where he gained experience in the clinical and electrodiagnostic evaluation of peripheral nerve disorders and developed his special interest in single-fiber electromyography, under the mentorship of Professor Erik Stalberg (Uppsala, Sweden). Currently, he works in one of the largest healthcare organizations in KSA, the National Neurosciences Institute, King Fahad Medical City, Riyadh. Other research and special interests of his include EMG-guided Botox injections for spasticity, neuro-intraoperative monitoring and sleep studies.

Abstract:

In the quest of “Chasing the Neuron”, localization of the peripheral nerve lesion is the primary goal of any neurophysiological study. Electrodiagnosis is an extension of the clinical neurological examination, without which one may find oneself lost in maze of peripheral neural axis. An array of different electrodiagnostic modalities are used to trace the neuron from the level of anterior horn cell in the spinal cord, to its end target organ, the post synaptic muscle. Nerve conduction studies are simple tests used to assess and localize the sensory and the motor nerves, with sparing of the sensory fibers in lesions that are pre-ganglionic, due to the residing of the posterior root ganglion away from the spinal foramina. However, in post-ganglionic lesions, both sensory and motor function is impaired, enabling to localize the lesion all along the plexus or the relevant peripheral nerve. Electromyography or needle EMG further helps in pinpointing the lesion, by mapping the presence of active denervating potentials in the muscles supplied by the affected nerve, assess for re-innervation as well as prognosticate recovery. By fatiguing the neuromuscular junction, in repetitive nerve stimulation, one can assess abnormalities of neuromuscular transmission and acquire information regarding a pre-synaptic or post-synaptic defect. Further specialized single-fiber electromyography studies enable to perform meticulous assessment of the jitter from single muscle fiber action potentials. Needle EMG is also the essence of differentiating a primary muscle origin disorder from an underlying neurogenic process. We summarize the use of electrodiagnostic modalities in the assessment of peripheral nerve disorders.