7^th Global Neurologists Annual Meeting on Neurology and Neuro Surgery August 22-24, 2016 Vienna, Austria

Biography:

Sarah Crawford received the Master’s Degree in Biochemistry from Princeton University in 1982 and a Ph.D. Degree from the Department of Biochemistry and Biophysics, Columbia University College of Physicians and Surgeons in 1987. I have been affiliated with Southern Connecticut State University for over 20 years, currently Full Professor in the Department of Biology where I teach Genetics and Medical Genetics, and direct a research laboratory in cancer biology. In 2013 I was awarded a patent by the US Patent Office for a novel cancer treatment for the brain cancer, glioblastoma.

Abstract:

The Quantitative Threshold Exposure (QTE) hypothesis is a multifactorial threshold model that accounts for the cumulative effects of risk factor exposure in both the causation of autism spectrum disorder (ASD) and its dramatic increase over the past 30 years. The QTE hypothesis proposes that ASD is triggered by the cumulative effects of high-level exposure to endogenous and environmental factors that act as antigens to impair normal immune system (IS) and associated central nervous system (CNS) functions during critical developmental stages. The quantitative threshold parameters that comprise a cumulative risk for the development of ASD are identified by the assessment of documented epidemiological factors that, in sum, determine the likelihood that ASD will occur as a result of their effects on critically integrated IS and CNS pathways active during prenatal, neo-natal and early childhood brain maturation. The model proposes an explanation for the relationship between critical developmental stages of brain/immune system development in conjunction with the quantitative effects of genetic and environmental risk factors that may interface with these critical developmental windows. This model may be useful even when the individual contributions of specific risk factors cannot be quantified, as it proposes that the combined quantitative level of exposure to risk factors for ASD rather than exposure to any one risk factor per se defines threshold occurrence rates.

Biography:

Czeslawa Kowal completed her PhD in the Institute of Organic Chemistry of the Polish Academy of Sciences, Warsaw, Poland, and her postdoctoral training in molecularbiology and in immunology at Columbia University and at the Albert Einstein College of Medicine New York. She has published 45 peer reviewed papers and book chaptersin reputed journals. She is a member of the American Association of Immunologists.

Abstract:

 Lupus is an autoimmune disease affecting primarily women in child bearing age. It is a multiorgan involvement disease, with frequent central nervous system (CNS) manifestation, most particularly, cognitive impairment. Lupus is characterized by the production of antinuclear autoantibodies and in particular, anti-dsDNA antibodies. We have created an animal model of CNS lupus in which autoantibodies cross-reactive with dsDNA and with the NMDA receptor (NMDAR) lead to an enhanced NMDAR activation and, at higher concentration to neuronal death when present in the brain parenchyma. We have shown that this requires breaching of the blood brain barrier. We have further demonstrated in the mouse model that the impact of these antibodies on neurons was concentration dependent and that at higher concentration, these antibodies promote neuronal excitotoxicity through enhanced mitochondrial permeability transition. In the model spatial recognition deficits are caused by the presence of these antibodies in the hippocampus. Structural analysis revealed a substantial reduction in dendritic processes and spines accompanied by a significant expansion of a place field size of surviving CA1 pyramidal. We and others have shown that the presence of these antibodies in the cerebrospinal fluid of lupus patients correlates with diffuse manifestations of CNS lupus. Recent studies of lupus patients harboring dsDNA and NMDAR reactive antibodies demonstrate an association with an impairment in spatial memory. This observation is in striking similarity to the mouse model.

Biography:

António Pais de Lacerda was graduated in medicine at the Medical School of the University of Lisbon (Portugal), and he has a master's degree in Medical Education. His current position is as intensive care consultant in an Intensive Care Unit (Hospital de Santa Maria); He is Assistant Professor of the Disciplines of "Introduction to Medicine", "Electrocardiography" and "Intensive Care Medicine". His main interests are on “pre- and post-graduate medical education ", "Medicine in the movies", "Sepsis" and "HIV / AIDS medicine." He has about 80 published papers, and two books on AIDS.

Abstract:

Human immunodeficiency virus (HIV) infection has been associated to premature atherosclerosis. Carotid intima-media thickness (CIMT) and pulsatility index (PI) accessed by carotid duplex ultrasonography (CDU) and transcranial Doppler (TCD), may be useful markers. Carotid and Cerebral circulation were evaluated by CDU and TCD in forty HIV-infected Caucasian men (mean age 49,4±5,9 years). CD4+ T-cell current and nadir counts, current and zenith viral load and duration of antiretroviral therapy (ART) were registered and cardiovascular risk scores were assessed. Multivariate regression analysis and Pearson's correlation coefficient were used. All men received ART and presented mean CD4+ count of 817±369 cells/mm3, (mean nadir: 242,8 ±158,2 cells/mm3), 95% had non-detectable viral load (mean zenith: 381.416±858.881 copies/mm3), 35% of men had history of high blood pressure, 35% dyslipidaemia, 7,5% diabetes, 80% tobacco consumption. Mean Framingham Risk Score was 8,5±6,6%; 35% presented low risk by SCORE, 55% moderate risk and 7,5% high risk. Mean ASCVD score was 7±4% at 10 years and 49±12% lifetime. 67.5% men had increased CIMT (mean 0,92±0,13mm), but none presented increased PI. No correlation was found between duration of infection, ART or cardiovascular risk scores with CDU or TCD data. However, a significantly positive association between a CD4+ nadir count <400 cells/mm3 and an increase of 0,12 in PI, was confirmed by regression analysis where CD4 categories showed significant effect over PI (p=.04). In this series, HIV infection showed an association with premature cerebral atherosclerosis, even at low cardiovascular risk scores. PI may be an early marker of atherosclerosis in HIV-infected people with CD4+ nadir <400 cells/mm3.

Biography:

Zhengqin Zhai has completed her Bachelor’s degree from Shandong University and now has been working for her Master’s degree in Peking Union Medical College.

Abstract:

Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the occurrence of ventricular arrhythmias after myocardial infarction. Here, we hypothesize that a novel pathway nerve stimulation - median nerve stimulation inhibit the occurrence of ventricular arrhythmias after myocardial infarction in rabbits. Two weeks after the ligation of mthe left coronary artery, 11 surviving New Zealand rabbits were randomized to median nerve stimulated (MI-MNS, n = 5) group and sham-stimulated (MI-SS, n = 6) group. Using an implantable electrical stimulator, we stimulated the bilateral median nerve for 2 weeks with the frequency of 5 HZ, width of 200ms, cycle of 10s on and 30s off, and the intensity of electrical stimulation was adjusted to the threshold of not resulting in the tremble of upper limbs. A holter was implanted to record the types and frequencies of arrhythmias. The treated rabbits had significantly lower percentage of ventricular arrhythmias (3.67% ± 1.73% vs. 6.69% ± 2.50%, p < 0.001) and lower norepinephrine (NE) level in blood (7.88 ± 2.34 pg/ml vs. 17.57 pg/ml± 11.72pg/ml, p = 0.01) than the untreated rabbits. Median nerve modulation markedly decreased the incidence of ventricular arrhythmias after myocardial infarction in rabbits through reducing the NE level in blood.

Biography:

Giovanni Antioco Putzu is working as professor in Neurology and Clinical Neurophysiology in Casa di Cura Sant’Elena, Italy. He has published more than 15 papers inreputed journals and has been serving as an editorial board member of repute.

Abstract:

We demonstrated, by the means of double immunochemistry technique, that TNF-alpha was localized in both axons and Schwann Cells, leading to demyelination and axonal in the peripheral nerve of patients with Guillain-Barré Syndrome (GBS, Putzu G.A. et al, J. Neurol. Sci, 2000). The pivotal role of pro-inflammatory cytokines such as IL-1Beta in GBS was also investigated. We present an original immunochemistry study with a panel of antibodies directed against TNF-alpha, INF-gamma, IL-1Beta, CD68, CD11, CD3 and C5b9 in the peripheral nerve of seventy-five patients affected by vasculitis. Sixty patients (27 males and 23 females, mean age 63 years) were classified as systemic vasculitic neuropathy (SVN) where as 15 patients (7 males and 8 females, mean age 52 years) had non systemic vasculitic neuropathy (NSVN). Results suggested a prevalent Th1 immune response in both SVN e NSVN. The presence of great amounts of TNF alpha and IL-1Beta into the vasculature determines a pro-coagulant effect with thrombosis of the vasa nervorum and hypoxia of the nervous fascicules. TNF-alpha was localized in axons as well, suggesting that it may be responsible for an axonal degeneration per se. Peripheral nerves of SNV e NSVN were immunoreactive to INF-gamma antibodies. This finding indirectly confirms the presence in the vasculature of IL-28A, a powerful pro-inflammatory cytokines. CD11, an antibody reacting with leucocytes and ICAM (Intercellular Adhesion Molecule) was also detected in the peripheral nerve of SVN and NSVN. Immunoreactivity to CD68 (macrophage antigen) and C5b9 (activated complement fraction) were also easily detected. In conclusion, immune response in SVN and NSVN is of Th 1 type (cellular). The role of TNF-alpha and cytokines is crucial in vascular thrombosis. Axonal degeneration may be the consequence of both hypoxia and direct toxic effect of TNF-alpha on axons. Moreover, pattern of immune response is not specific in SVN and NSVN

Biography:

Weimin Yang has completed his PhD from Sichuan University and visiter scholor studies from Melbourne University. He is the professor in Dept. of Neurology, First Affiliated Hospital of Zhengzhou University, master tutor, innovative talents of Henan Province Health Sciences and Technology. His research work mainly related to clinical features of Chinese stroke patients, stroke register, dementia, and systematic reviews of therapies from China. He has published more than 25 papers in reputed journals.

Abstract:

Background: Intracerebral hemorrhage (ICH) is a significant contributor to global health-related morbidity and mortality. Due to improved recognition and treatment of atrial fibrillation by antithrombotics, there is an increase in proportion of ICH caused by warfarin and novel oral anticoagulants. However, the relationship between anticoagulation intensity and hematoma expansion remains unclear. We aimed to investigate the effects of INR on hematoma expansion post ICH.

Methods: We conducted a retrospective study of all patients hospitalized for ICH at a single institution from January 1, 2008 and August 1, 2014. Hematoma volumes on initial CT scans and repeat CT scans were analyzed by the AxBxC/2 method. Univariate analysis was used to compare baseline characteristics and median regression analysis was performed to estimate the effects of INR and hematoma volume changes.

Results: We included 224 consecutive ICH patients. Median age (IQR) was 68.5 years (17.0), 60.3% were male, median presentation Glasgow Coma Scale (GCS) (IQR) was 14.0 (4.0), median volume (IQR) of the first CT was 11.7ml (25.6), median INR (IQR) was 1.1 (0.2). We showed that INR and time lapsed between first CT and second CT were independent risk factors to hematoma volume change, adjusting for baseline hematoma volume and time. For each 1.0 increase in INR was associated with hematoma volume increased by 2.4ml (p = 0.015).

Conclusions: We showed that high INR was associated with hematoma growth post ICH. However, the effects of reversal anticoagulation.

Biography:

Lenka Maruscakova, MD. was graduaded in General Medicine at the School of Medicine, Comenius University Bratislava, Slovakia. She does her postgradual studies at Institute of Immunology School of Medicine, Comenius University Bratislava, Slovakia. Her PhD. thesis is devoted to the inflammatory markers in brain tumors. Her scientific work is multidisciplionary approach connecting field of immunology, oncology and neurology.

Abstract:

Immune cells and molecules in tumor microenvironment are crucial in tumorigenesis. Inflammation is known as one of hallmarks of cancer and is considered as an protumorigenic factor. Glioma tumor microenvironment glioma still needs deeper insight into its immunological characteristics. Both local and systemic chronic low grade inflammatory response are operative for correlation with gliomas grading and their prognosis. Complex network of immune signals and pathways is in intricate background of most of cancer hallmarks. This concept is an intersection of three huge research fields: immunology, oncology and neurology. Cancer immunology has a perspective in complex approach to diagnosis of gliomas. There is an appealing importance of establishing immune molecules in gliomas. TREM-1 (Triggering receptor expressed on myelocytes) is an inflammation amplifier, hovewer its role in glioma remains still unclear. The aim of our study is to establish the expression of TREM-1 in glioma tissues and to correlate it with staging, grading and other laboratory parameters. Establishing of TREM-1 expression could have a promissing role in pathophysiology of gliomas. Our preliminary results show densely infiltrating TREM-1+ immune cells in tumor tissue. At signal pathways level, inflammation is interconnect with molecules related to hypoxia. Cross-talk of inflammation and hypoxia becomes more obvious in glioma as well. Consideration of relations dynamics is also necessary. But, deep understanding of their signal network in glioma tumorigenesis 

Biography:

Zhengqin Zhai has completed her Bachelor’s degree from Shandong University and now has been working for her Master’s degree in Peking Union Medical College.

Abstract:

Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the occurrence of ventricular arrhythmias after myocardial infarction. Here, we hypothesize that a novel pathway nerve stimulation - median nerve stimulation inhibit the occurrence of ventricular arrhythmias after myocardial infarction in rabbits. Two weeks after the ligation of mthe left coronary artery, 11 surviving New Zealand rabbits were randomized to median nerve stimulated (MI-MNS, n = 5) group and sham-stimulated (MI-SS, n = 6) group. Using an implantable electrical stimulator, we stimulated the bilateral median nerve for 2 weeks with the frequency of 5 HZ, width of 200ms, cycle of 10s on and 30s off, and the intensity of electrical stimulation was adjusted to the threshold of not resulting in the tremble of upper limbs. A holter was implanted to record the types and frequencies of arrhythmias. The treated rabbits had significantly lower percentage of ventricular arrhythmias (3.67% ± 1.73% vs. 6.69% ± 2.50%, p < 0.001) and lower norepinephrine (NE) level in blood (7.88 ± 2.34 pg/ml vs. 17.57 pg/ml± 11.72pg/ml, p = 0.01) than the untreated rabbits. Median nerve modulation markedly decreased the incidence of ventricular arrhythmias after myocardial infarction in rabbits through reducing the NE level in blood.

Biography:

Teena Shetty is a Fulbright scholar who received her medical degree and bachelor’s degree with honours from Brown University and her master of philosophy degree in medicine from the University of Cambridge. Her residency was completed at Weill Cornell Medical College, New York-Presbyterian Hospital. Dr. Shetty received her fellowship training in neuromuscular diseases at Harvard Medical School, Brigham and Women’s Hospital and in neuromuscular diseases and intraoperative monitoring at Hospital for Special Surgery. Dr. Teena Shetty is now a neurologist at Hospital for Special Surgery and is triple board-certified in neurology, neuromuscular medicine, and electro diagnostic medicine. Her research interests include concussion, post-operative neuropathies, muscle diseases, and intraoperative monitoring, and she has authored more than 30 publications on these topics.

Abstract:

Historically, routine types of neurological imaging for mTBI include CT and Conventional MRI, both of which are usually normal in mild TBI (mTBI). Newer MRI methods may demonstrate more abnormalities following mTBI than just CT or Conventiona MRI alone (Brody et al 2015). These include, but are not limited to, SWI, DTI, rs-fMRI, ASL and Volumetry. Susceptibility Weighted Imaging (SWI) uses contrast to highlight differences between tissues that can show changes in blood products in the brain. Diffusion Tensor Imaging (DTI) can detect brain abnormalities in white matter through its sensitivity to microstructural axonal injury. Resting State Functional MRI (rs-fMRI) measures changes in blood perfusion to determine if pathways of communication within the brain  have been disrupted. ASL (arterial spin labelling) uses spatially selective inversion of inflowing arterial blood as a method to label blood flow and measure perfusion. Lastly, volumetric MRI measures the volume and structure of regions in the brain and can detect changes in the volume of gray matter that may result from mTBI. These specific types of imaging can be incorporated into research in order to learn more about concussions, their diagnosis, and their prognosis. This is the case for the GE-NFL Study on Advanced MRI Applications for mild TBI. By utilizing a research pack for neurological imaging that includes SWI, DTI, Volumetric T1, ASL, and rs-fMRI, researchers have been able to detect abnormalities, including white matter lesions, in the brains of several patients who have suffered from mTBI. Overall, neuroimaging is evolving such that white matter abnormalities, changes in gray matter volume, and blood perfusion in the brains of mTBI patients may be visualized. However, these scans cannot be used conclusively and these techniques are limited to research tools at this time. Therefore, continued study is necessary to further validate these software techniques

Biography:

Dr. 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.

Abstract:

Aortic arch plaque (AAP) is associated with stroke and is a potential embolic source. Amarenco reported an increase of recurrent stroke in patients with complex (AAP) plaques >4mm thickness compared to simple plaques. Plaque heterogeneity and mobility play a role. We developed a noninvasive method to image AAP with B-mode sonography through the supraclavicular fossa to determine whether AAP is an etiology of stroke. B-mode correlation with transesophageal echocardiography (TEE) in 37 patients showed 93.75% sensitivity, 80.95% specifiticy, 78.95% positive predictive value and 94.40% negative predictive value. In 500 consecutive patients referred for carotid duplex, the arch was visualized completely in 468, partially in 27 and not visualized in 15. Complex plaques were seen in 40 symptomatic patients and 64 asymptomatic patients, simple plaques in 131 symptomatic patients and 260 asymptomatic patients, difference not significant. Excluding patients with ipsilateral carotid stenosis and atrial fibrillation, complex plaques were seen in 24 symptomatic patients and 31 asymptomatic patients, simple plaques in 90 symptomatic patients and 188 asymptomatic patients, p = 0.075. Among patients with complex plaques, 19 heterogeneous plaques were symptomatic and 15 asymptomatic, 21 patients with homogeneous plaques were symptomatic and 46 asymptomatic p=0.037. One hundred sequential studies in 89 patients over 18 months were performed to measure a change >0.5mm. For 46 simple plaques, 77% had no growth, 10% regressed and 13% progressed. For 27 complex plaques 48% had no growth, 38% regressed and 14% progressed. Intimal thickness of AAP in 504 patients correlated linearly with presence of coronary artery disease r=0.97, p<0.001 (0-1mm 16%, 1-2mm 38%, 2-3mm 56%, 3-4mm 58%, 4-5mm 79%, 5-6mm 89%). CONCLUSIONS: Aortic arch plaques are relatively stable. High risk aortic arch plaques are associated with heterogeneous morphology. Complex AAP are associated with generalized atherosclerosis including coronary artery disease. Sequential noninvasive imaging of AAP can have value in future studies of therapy to prevent stroke from AAP. The proposed mechanism of embolism from carotid and aortic arch plaque is plaque rupture. Ultrasound videos of carotid and aortic arch plaque rupture in acute stroke patients will be shown.

Biography:

Michael Chopp is Vice Chairman, Department of Neurology, Scientific Director , Neurosciences Institute, Zoltan J. Kovacs Chair in Neuroscience Research at Henry Ford Hospital, Detroit Michigan, and a Distinguished Professor of Physics at Oakland University, Rochester Michigan. He has published widely (>650 peer reviewed publications) in the area of neurorestorative and neuroprotective therapies for stroke, traumatic brain injury and neurodegenerative diseases. He has also served on many NIH study sections, and as a consultant to the pharmaceutical industry. He is the recipient of major awards and recognition for his research, including the 2015 Willis Lecture from the American Heart Association, 2012 Lecture of Excellence at the World Stroke Organization and the Abraham White Distinguished Science Award from George Washington University.

Abstract:

The ability to regulate and modulate intercellular communication may provide the basis for the treatment of neurological injury, neurodegenerative diseases and stroke. Exosomes are small (30-100 nm) endosomal generated particles consisting of a complex lipid membrane and contain proteins, RNAs,mRNAs and microRNAs (miRNAs). Nearly all cells generate exosomes, and these small lipid containers are ubiquitous in biological systems and provide an intercellular communications network which regulate cellular function. Exosomes mediate intercellular communication by transferring proteins, lipids, and genomic materials including mRNAs and miRNAs between source and target cells In this presentation, I will describe our work on the treatment of stroke, traumatic brain injury and diabetic peripheral neuropathy with exosomes, with a focus on the transfer of microRNA (miR) content within the exosomes to recipient cells. miRs are 20-25 nucleotide non coding RNA which regulate gene translation . They act as major molecular switches and are post transcriptional regulators of protein production and simultaneously impact multiple molecular pathways and signaling within cells. We have found that cell-based therapies promote neurological recovery and promote neurovascular remodeling by transferring exosomes to recipient cells. Thus, we have harvested exosomes by means of ultracentrifugation of biochemical methods from a variety of cells, and directly employed these exosomes by intravenous administration for stroke ,TBI and peripheral neuropathy to promote neurological recovery. Exosome treatment was highly effective in promoting neurovascular remodeling and enhancing neurological recovery after stroke, TBI, and peripheral neuropathy. Our studies demonstrate that exosomes may provide effective therapy for the treatment of neurological diseases and injury.

Biography:

Abstract:

Neurodegenerative diseases (NDs) such as Alzheimer’s disease [1,2] and Parkinson disease [3] are among the big challenges facing the researches and the clinical professionals. NDs have complex mechanism including pathways that are yet to be elucidated. Each of these diseases is often studiesseparately and investigated towards explaining the mechanisms and finding potential therapies of one disease. Changing such approach might be a way to improve the data we obtain. Indeed, many common features exist between the NDs. Therefore, focusing on such common features and mechanisms will allow us to extrapolate the obtained results and explain a pathway involved in more than one neurodegenerative disease and thus find out potential therapies for more than on neurodegenerative disease. Such methodologies still require further elucidation of the common features linking the divers’ neurodegenerative disease and whether they are such links are the results of common underlying pathways or only similar symptoms or phenotypes. These needs collaborations between experts in different fields including the concerned NDs and always study each neurodegenerative disease within the context of the common features shared between more than a neurodegenerative disease and complete the data by cell culture studies results [4], pharmacology [5-10] and toxicology [11,12] to reach the final goal which is identify efficient therapies. Such approaches will optimize the efforts aiming to understand the NDs and treat them by reducing the research cost, efforts and time. For building an animal model of a neurodegenerative disease such as Alzheimer’s disease [13] expressing a specific feature will contribute to study all the NDs that include that specific feature within its pathogenesis. Importantly, this concept is further strengthened by several facts such as the physiology of the brain that constitutes of a network within which the neurotransmitters are in continuous interactions [14] and the common molecular basics [15] related to the G protein coupled receptors [16] that are of a great importance in both neurophysiology [17] and pharmacotherapy [18-20]. In addition, other non-degenerative diseases share also similar mechanisms or pathways with some NDs which means that the range of extrapolation of the common features shared by some neurodegenerative disease might also include some non-NDs.

Biography:

Sylvain Lanthier trained in optometry, medicine, ophthalmology and neurology at University of Montreal. During his neurovascular fellowship, he studied unusual causes of stroke at the University of Toronto and clinical epidemiology and biostatistics at McMaster University. He is Associate Professor of Medicine, Department of Neurosciences at the University of Montreal and Stroke Neurologist at the Centre hospitalier de l’Université de Montréal. Dr. Lanthier published more than 40 research articles and book chapters on cerebrovascular disease. His main research interests are stroke in the young and CNS vasculitis. He is the lead-PI of the INTERSPACE.

Abstract:

Primary angiitis of the CNS (PACNS) is an idiopathic, single-organ vasculitis of small and medium-sized vessels. Diagnosis of PACNS is a real challenge because it is rarer than several other potential mimicking conditions. Clinical presentation are variable, including persistent headaches, cognitive decline, multifocal deficits and seizures. Brain lesions on MRI and inflammation of the cerebrospinal fluid are common findings, whereas angiographic changes may be documented mainly when medium-sized arteries are affected. None of these manifestations are specific for PACNS. CNS biopsy can prove the diagnosis when small arteries are involved, but this procedure is invasive and associated with potential false-negative results due to skipped lesions. Complementarily, gadolinium-enhancement of medium-sized arteries can be documented by high-resolution MRI. Treatment of PACNS is also challenging, aiming at minimizing the risks of treatment failure and recurrent vasculitis due to insufficient immunosuppression while avoiding adverse effects of potent immunosuppressant agents. Other single-organ vasculitides of the CNS comprise the amyloid-beta-related angiitis (ABRA) and the inflammatory form of cerebral amyloid angiopathy (iCAA). The nosological limits of PACNS, ABRA and iCAA remain misunderstood. The INTERnational Study on Primary Angiitis of the CEntral nervous system (INTERSPACE) is an international, multi-center, prospective, currently ongoing, cohort study. INTERSPACE was designed to describe clinical manifestations, investigation results, diagnostic processes, misdiagnoses, treatments and outcomes of clinically-suspected or biopsy-proven PACNS. Its primary objective is to identify predictors of death or dependence after 1 year of clinical follow-up. To join INTERSPACE, study investigators are invited to contact the Coordination Centre: sylanthier@gmail.com.

Biography:

Dr. Marcelo Kauffman is the Head of the Neurogenetics Clinic and Laboratory at the JM Ramos Mejia Hospital, in Buenos Aires, Argentina. He obtained his MD, MSc and PhD degrees from the University of Buenos Aires and from the University Pablo de Olavide in Spain. He completed his Residency in Neurology at the JM Ramos Mejia Hospital in Buenos Aires. He is a researcher at the Argentine’s National Science Council (CONICET) and Assistant Professor of Neurology at the University of Buenos Aires, School of Medicine. His clinical and research interests include the diagnosis, management and treatment of neurogenetic disorders. He has received many clinical and scientific awards and authored more than 40 peer-review papers, mainly in the field of neurogenetic diseases

Abstract:

As a whole neurogenetic diseases are a common group of neurological disorders. However, the recognition and molecular diagnosis of these disorders is not always straightforward. Besides, there is a paucity of information regarding the diagnostic yield that specialized neurogenetic clinics could obtain. We performed a prospective, observational, analytical study of the patients seen in a neurogenetic clinic at a tertiary medical centre to assess the diagnostic yield of a comprehensive diagnostic evaluation that included a personalized clinical assessment along with traditional and next-generation sequencing diagnostic tests. We included a cohort of 424 patients from May 2008 to July 2015. For sub-group analysis we selected a sample of patients whose main complaint was the presence of progressive ataxia, to whom we applied a systematic molecular diagnostic algorithm. Overall, a diagnostic mutation was identified in 28% of our cohort. However, if we only considered those patients where a molecular test could be performed, the success rate rises to 45%. We obtained diagnostic yields of 23•5 and 57•5% in the global group of ataxic patients and in the subset of ataxic patients with a positive family history, respectively. Thus, about a third of patients evaluated in a neurogenetic clinic could be successfully diagnosed.

Biography:

Dr. Manconi is the Head of the Service at the Sleep and Epilepsy Centre of the Neurocenter of Southern Switzerland, Lugano, Switzerland. Mauro Manconi earned his medical degree (1997) at the University of Bologna (Italy) with honour, discussing a thesis on Central Alveolar Hypoventilation. He completed his specialization in Neurology (2002) at the University of Ferrara (Italy) with honour, discussing a thesis on Restless Syndrome and Pregnancy. He defended his PhD in Sleep Medicine (2005) at the University of Bologna (Italy) with honour on REM Behaviour Disorder. For 10 years he served as clinical researcher at the Sleep Lab of Scientific Institute of San Raffaele, Milan (Italy). Dr. Manconi served for 1 year as Visiting Professor at the Circadian Rodent Lab of the Wisconsin Medical College, Milwaukee (WI, USA), where he obtained the “Excellent in Sleep Research Award 2006 for his innovative and leading research activity in developing a pharmacogenetic rodent model for Restless Legs Syndrome. He is currently involved in clinical and basic research in sleep field, with particular interest in sleep related motor disorders. He has written over 100 publications and 1 book and is member of various International Sleep Societies.

Abstract:

Restless leg syndrome (RLS) is an often under diagnosed sleep-related sensorimotor disorder which affects up to 10% of adult general population, characterized by uncomfortable sensations in the legs, which begins or worsens during rest, improves or disappears with movement, and occurs or worsens in the evening or at night. RLS is often associated to insomnia and reduced quality of life. In more than 80% of patients, the polysomnography unmasks periodic leg movements (PLM) during sleep, which are repetitive leg jerks characterized by a triple flexion movement of the lower limbs, usually associated to electroencephalographic arousals and to an increasing of the heart rate, which can contribute to sleep disruption. The idiopathic one is the most common form of RLS and can be inherited as an autosomal dominant trait. Recently, two large genome-wide scan studies recognized three genomic regions encoding the intronic variants of the genes MEIS 1, BTBD9 and MAP2K5. Even though the pathogenesis of the RLS is still unknown, there are several pieces of evidence that address to a possible dysfunction of the descending dopaminergic neurons from the hypothalamic A11 region to the intermediolateral and dorsal spinal gray matter. RLS worsens with antidopaminergic treatment, can be induced by hyposideremia (iron is the coenzyme of the tyrosine-hydroxylase, the limiting enzyme in the dopamine synthesis), may be associated with Parkinson diseases, and shows a circadian trend of the symptoms and PLM distribution which is inversely related to the levels of blood and cerebro-spinal fluid dopamine. As well as in reward and cognitive processes, dopamine is also strongly implicated in regulation of locomotor activity and movement in general. Mainly, the dopaminergic hypothesis in RLS is supported by the fact that both RLS and PLM respond dramatically to dopamine-agonists medication, even at very low dosages and since the first night of administration.

Biography:

Abstract:

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). It became known as Devic disease following a seminal 1894 report. Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The core clinical characteristics required for patients with NMOSD withAQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. The consensus definition of NMOSD unifies traditional NMO and modern NMOSD definitions. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The IPND criteria are expected to facilitate more comprehensive and comparable epidemiologic studies by supplying a uniform case definition and a glossary of defined terms. We will be reviewing advances in this field .

Biography:

Yun Zhou is Assistant Professor at the Russell H. Morgan Department of Radiology and Radiological Science, and Guest Professor of Peking University First Hospital. He obtained his M.S. in Biomathematics and Ph.D. in Biomedical Physics from University of California at Los Angeles.

Abstract:

Brain PET is a well-established quantitative functional imaging technique to measure physiological and biochemical process. As recent advances in hybrid imaging technology, such as PET-CT and PET-MRI, for whole-body PET imaging, there are urgent needs to develop and validate technologies for quantitative whole-body PET from data acquisition to quantification. The fundamentals of quantitative PET developed in last three decades which include kinetic modeling approach and parametric imaging algorithms will be briefly reviewed. Recent developments in quantitative PET imaging on dopamine and serotonin receptors and transporters will be highlighted. Tremendous efforts have been made to extend quantitative brain or organ-specific PET to dynamic whole-body PET in last few years. We investigated the feasibility of quantitative dynamic whole-body PET via multi-bed multi-pass technology. Optimization in data acquisition and quantification were studied by both computer simulation and an ongoing multi-center multi-tracer dynamic whole-body PET project. The potentials and challenges in quantitative whole-body PET in clinical diagnosis, monitoring disease progression, responses to treatments or psychological/ pharmacological stimulations will be discussed with our promising results.

Biography:

Jianhua Zhang has completed his M.S. in 2004 and M.D. studies in 2012 from Peking University, majoring in Radiology and Nuclear Medicine. He joined the faculty of nuclear medicine at Peking University First Hospital.in 2004 and now is the associate professor. He has published more than 20 papers in journals and 20 chapters in proceedings and medical textbooks. The research interests of Dr. Zhang include application of positron emission tomography (PET) in studies of tumors, especially the lymphoma, and quantitve analysis. He has been involved in teaching of more than 30 residents.

Abstract:

Richter’s transformation (RT, Richter’s syndrome) was first described by Maurice Richter as the development of an aggressive large-cell lymphoma in the setting of underlying small lymphocytic lymphoma /chronic lymphocytic leukemia (SLL/CLL). We try to investigate the role of in detection of RT of SLL/CLL. Twelve patients with SLL/CLL underwent 18F-FDG PET/CT between Jul 2010 and Nov 2015 were retrospectively analyzed. FDG avid lesions with a maximum standardized uptake value (SUVmax) of greater than 5 were considered highly suggestive of RT. The diagnosis of RT was based on the histopathological examination. All patients (8 males and 4 females) had the history of SLL/CLL ranged from 2 years to 11 years. Four patients underwent RT to diffuse large B-cell lymphoma, PET/CT detected sites of increased FDG uptake with SUVmax ＞5 in 3 patients(3/4, 75%), 1 patient has false-negative PET/CT findings. No patient had false-positive PET/CT findings and PET/CT correctly excluded RT in the other 8 patients. The overall sensitivity, specificity and accuracy of PET/CT for RT of SLL/CLL were 75%, 100% and 91.6%, respectively. According to the preliminary data, 18F-FDG PET/CT has high accuracy for detection of RT of SLL/CLL. PET/CT can exclude the diagnosis of RT with a high degree of confidence in patients with SLL/CLL. 

Biography:

Rong Fu Wang has completed his MD at the age of 27 years from Fujian Medical University in 1982, postdoctoral studies from Paris V University School of Medicine in 1993 and his PhD at the age of 40 years from Toulous IIl University in 1995. He is the director of Department of Nuclear Medicine, Peking University Health Science Center. The research interests of Dr. Wang include experimental study and clinical application of molecular and clinical nuclear medicine. He has published more than 400 papers in reputed journals and has been serving as many editorial board member of reputed journals at home and abroad. He has published 3 monographs, and has got 3 patents of invention and 3 provincial and ministerial Awards.

Abstract:

18F-FDG uptake rate constant Ki is a most interested and commonly used parameter for absolute quantification of 18F-FDG PET/CT. Ki is usually estimated by fitting a kinetic model with plasma input function (PIF) to the measured dynamic PET data. The need for arterial blood sampling to measure PIF (mPIF) is a main barrier to estimate Ki for clinical 18F-FDG PET. Two existing noninvasive PIF estimation methods, image derived PIF and simultaneous fitting method with kinetic model and parametric PIF, require image data to be acquired continuously and immediately post tracer injection. The objective of the study is to validate and optimize a generalized population-based PIF estimation method for noninvasive quantification of dynamic 18F-FDG PET for sparsely sampled PIF. Eight 60-min 27-frame monkey dynamic 18F-FDG PET studies were collected from a Philips Gemini GXL PET/CT with 3D data acquisition mode. Total 34 arterial blood samples were taken during PET scan as: 22 samples for the first 4 min, and followed by sampling at 5, 6, 8, 10, 12, 15, 20, 25, 30, 40, 50 and 60 min. Time activity curves (TACs) of 7 cerebral regions of interests (ROIs) were generated from each study. A generalized population-based approach to recover full kinetics of the PIF from sparsely sampled blood data is proposed. The estimated PIF (ePIF) from the incomplete PIF sampling data was determined by interpolation and extrapolation using scale-calibrated population mean of normalized PIFs. The optimal blood sampling scheme with given sample size m was determined by maximizing coefficient coefficients of Ki estimates between the Kis from measured PIF (mPIF) and estimated PIF (ePIF). The leave-two-out cross validation was performed. The linear correlations between the Ki estimates from the ePIF (with optimal sampling scheme) and those from the mPIF were: Ki(ePIF; 1 sample at 40 min) = 1.015Ki(mPIF) -0.000, R2 = 0.974; Ki(ePIF; 2 samples at 25 and 50 min) = 1.029Ki(mPIF) - 0.000, R2 = 0.985; Ki(ePIF; 3 samples at 8, 20, and 50 min) = 1.039Ki(mPIF) - 0.001, R2= 0.993; and Ki(ePIF; 4 samples at 8,12, 25, 40, and 55 min) = 1.02Ki(mPIF)-0.000, R2=0.997. The correlations of R2 from leave-2-out validation study were 0.978±0.007, 0.990±0.006, and 0.996±0.003 (mean ±SD) for 1, 2, and 3 samples of optimal sampling scheme, respectively. The generalized population-based PIF estimation method is a reliable method to estimate PIFs from incomplete blood sampling data for quantification of dynamic 18F-FDG PET using the Gjedde-Patlak plot. 

Biography:

Zhoulei Li has completed her PhD in 2013 from Ludwig-Maximilians-University of Munich and postdoctoral studies from technical university Munich. She has published more than 10 papers in reputed journals. She is a research leader, managing a pharmaceutical project from Helmholtz Center Munich. Before that, She was a postdoc researcher, managed the clinical research lab at nuclear medicine of technical university Munich, supervised research staff and graduate students. She has extensive hands on experience on molecular imaging. Her research focuses on monitoring progress of cancer therapy and developing biomarker for cancer therapy.

Abstract:

The prognosis of relapsed or refractory aggressive lymphoma is poor. The huge variety of currently evolving targeted treatment approaches would benefit from tools for early prediction of response or resistance. Molecular imaging is recently recognized as a tool that can improve every facet of cancer care. PET images biochemical or physiologic phenomena in comparison with computed tomography (CT) or magnetic resonance imaging (MRI), which show anatomic details. PET imaging would predict areas of abnormal metabolic behaviour of cancers in vivo, and the addition of CT imaging underlines the site of malignancy. More accurate andprecise interpretation of cancer lesions can therefore be performed by PET/CT imaging than PET or CT imaging alone. We used various lymphoma cell lines (ALCL, DLBCL, MCL, Myc-induced murine lymphoma etc.) to evaluate therapeutic effect of different anti-cancer drugs in vitro by molecular biological and biochemical methods. Micro-FDG- and/or FLT-positron emission tomography (PET) or PET/CT imaging studies were carried out with the suitable xenograft or transgenic mouse models to assess early treatment response to anti-cancer therapy in vivo. Interestingly, we detected a significant reduction of FLT-uptake in ALCL bearing animals using targeted drug therapy compared with baseline as early as 2 days after initiation of targeted therapy. Immunostaining showed a decrease in Ki-67 and an increase in cleaved caspase-3 staining. Additionally, the detection of therapeutic response of other aggressive cancer was proved to be highly correlated with other in vito and in vivo data, suggests that PET/CT is a suitable method for detection of therapeutic respons on cancer. 

Biography:

Tang graduated from University of South China and received her master’s degree in plastic and reconstruction surgery form Peking Union Medical College. She finished her surgical residency training and became a breast surgery specialist in 2011. After that, she has been working as a postdoctoral fellow at Surgical Oncology of Massachusetts General Hospital.She has published peer reviewed journal papers. Her interests include oncoplastic breast procedures, breast cancer shaved cavity margins, nipple sparing mastectomy, and novel breast imaging methods

Abstract:

Intraoperative specimen imaging is commonly performed to confirm complete excision breast lesions, but has false positive and false negative rates that lead to incorrect specimen assessment in 21-44% of cases.Micro-CT provides non-invasive, highly quantitative imaging in small specimens within a few minutes. We explored the use of micro-CT for intraoperative assessment of a variety of breast specimens. Excised breast specimens, including lumpectomy specimens, shaved cavity margins(SCM), mastectomy specimens and axillary lymph nodes, were evaluated with a table top micro-CT scanner, Skyscan 1173 (Skyscan, Belgium), with a 40-130kV,8W X-ray source. Scanning for 7 minutes and reconstruction for another 7 minutes provided desired resolution in breast specimens. In lumpectomy specimens, micro-CT could clearly visualize orienting sutures and see the location of tumour masses and associated calcifications relative to specimen margins. In separately excised cavity margin specimens, micro-CT visualized tumour masses and calcifications that indicated the need for additional tissue excision. Micro-CT provided detailed images of axillary lymph nodes and their vessels’ 3D structure. 103 SCM from 26 lumpectomies were scanned and compared with histopathology results. Margin status by micro-CT was concordant with histopathology in 86/103 (83%) SCM. Micro-CT had 73% sensitivity, 85% specificity, 46% positive predictive value, and 95% negative predictive value of SCM. 5/26(19%) case required a re-excision based on the final margin status, micro-CT could identify 3 out of these 5 cases intra operatively.  Micro-CT is a potentially useful tool for assessment of breast cancer specimens, allowing real-time analysis of breast lumpectomy specimens or cavity shaved margins.

Biography:

Jianhua Zhang has completed his M.S. in 2004 and M.D. studies in 2012 from Peking University, majoring in Radiology and Nuclear Medicine. He joined the faculty of nuclear medicine at Peking University First Hospital.in 2004 and now is the associate professor. He has published more than 20 papers in journals and 20 chapters in proceedings and medical textbooks. The research interests of Dr. Zhang include application of positron emission tomography (PET) in studies of tumors, especially the lymphoma, and quantitve analysis. He has been involved in teaching of more than 30 residents.

Abstract:

18F-FDG PET/CT imaging has become a crucial component of oncological management for a wide variety of malignancies and is routinely used in staging, restaging and treatment response assessment tasks. Compared to qualitative method and semi-quantitative method, quantitative method is more accurate and can overcome the limitations of the routine methods, but it is more complicated on the management of many cancer patients. As for the quantitative method, plasma input function and FDG influx rate constant (Ki) are indispensable. An emphasis in the present work is to develop non-invasive plasma input function estimation techniques in order to facilitate clinical acceptance. Image derived input function method will be studied and validated in the novel context of whole body dynamically-acquired images to facilitate parametric imaging. The present work is expected to significantly enhance the capability of dynamic whole body FDG PET/CT imaging to quantify the kinetics of FDG, and in turn, has the long-term potential to significantly enhance diagnostic, prognostic and treatment response monitoring capabilities of the FDG PET imaging modality and to fundamentally alter routine clinical practice.