Day 1 :
Keynote Forum
Gjumrakch Aliev
GALLY†International Biomedical Research Institute Inc., San Antonio, TX, USA
Keynote: Implication of the Multitarget Therapies in the Context of the Aged Associated Oxidative Stress Induced Cellular and Subcellular Hypoperfusion, and Mitochondrial DNA deletion During the Development and Maturation of Alzheimer Disease: past present future
Time : 10:00-11:00
Biography:
Dr. Gjumrakch Aliev, MD, PhD, President “GALLY” International Biomedical Research Institute Inc., San Antonio, Texas, USA. He also hold appointment with the University of Atlanta, Georgia, USA as a Professor of Cardiovascular, Neuropathology, Gerontology, Health Science and Healthcare Administration, and as a Leading Scientist , Institute of Physiologically Active Compounds, Russian Academy of Sciences, Moscow Region, Chernogolovka, Russian Federation. He received his MD in 1982, from the Baku Medical University (former USSR) with cum laude. Then he accomplished his PhD in Cardiovascular Diseases from the prestigious Russian Academy of the Medical Sciences, Moscow, Russia in 1988 with cum laude. He received postdoctoral training with Professor G. Burnstock in the University College of the London. He is an outstanding teacher, scholar, and a renowned scientist in the area of cellular molecular physiology, and cardiovascular, and neurodegeneration-mediated pathologies including Alzheimer disease (AD). He is nationally and internationally reputed in his area. He is one of most cited authors in his fields with high impact factors.
Abstract:
Background and Hypothesis: Oxidative stress induced cerebral hypoperfusion and mitochondrial failure appears to be a key pathogenic factor in the development of age-associated diseases, triggering mild cognitive impairment and eventual conversion to Alzheimer disease (AD). Mitochondrial integrity is associated with cellular viability.
Goal: We studied cellular and subcellular features of hippocampal neurons and microvessel mitochondrial lesions, oxidative stress markers and protein immunoreactivity in animal models that mimic MCI and/or AD. In addition, we studied the effects of dietary antioxidant treatment on neuronal mitochondrial ultrastructure in rats. The goals of the proposed study are to determine the role of mitochondria failure and neuronal damage during the maturation of AD-like pathology in rats and transgenic mice overexpressing either amyloid β precursor protein (AßPP).
Methods: In this project we applied the following methods: transmission electron microscopy (TEM) qualitative analysis; EM pre-embedding immunogold cytochemistry using probes for human wild type, 5kb deleted and mouse mtDNA and antibodies against cytochrome c oxidase. Quantitative morphometric analysis of the degree of mitochondrial lesions.
Summary of Results: there was a significantly higher degree of mitochondrial damage and mitochondrial DNA overproliferation and deletion in neurons and cerebrovascular wall cells in transgenic mice and aged untreated rats in comparison to age-matched controls and non-treated subjects. Mitochondrial abnormalities are associated with atherosclerotic lesions of brain microvessels.
Conclusion: based on this results our conclusion is that changes in mitochondrial morphology and mitochondrial DNA coexist with metabolic dysfunction in AD mice and age-associated neurodegeneration and may serve as diagnostic markers and treatment targets
Keynote Forum
Natasa Radojkovic Gligic
University of Belgrade, Serbia
Keynote: Epileptic phenomena, differential diagnosis, delirium in case of an acute stroke patients that have been diagnosed with vascular dementia in the past
Time : 11:20-12:05
Biography:
I was born in 1964, received my medical degree from the Faculty of Medicine at the University of Belgrade in 1989. In 1994, I became a neurologist. Over the course of my career, I took part in many additional courses, most notably: - a 6 month course in electroencephalography at the Institute of Neurology(1991) - a pediatric and neonatal EEG course at the University Hospital for pediatrics (1996) - ultrasonography of main head and neck blood vessels and transcranial doppler training (2000) In regards to my work experience, I have worked from 1989 until 2002 at the General Hospital in Pozarevac. In 2002, I moved to the Hospital for cerebrovascular diseases “Sveti Sava” in Belgrade, and have been there since. Today, my work mainly revolves around the latest treatments of blood vessel thrombosis, thrombolysis and thrombectomy. Since 2008, I have published numerous research papers both domestically and internationally. In 2014 I obtained the title of a primarius, the highest domestic distinction for a clinical physician.
Abstract:
Patients who have psychiatric illness, dementia or brain tumors can go through real diagnostic procedures and therapy for a long time. Non-convulsive epileptic seizures are often unrecogniozied as transient confusional conditions in younger patients,which requires the introduction of electrocenography into the protocol in our patients.
The main aim of this research is to monitor patients with dementia, with MMSE score from 16 to 22, when the patients’ age is between 68 and 75 years. All of the patients had vascular dementia earlier and were women. We conducted protocol diagnostics and gave psychiatric therapy that they otherwise received before arriving in our institution and consult. The protocol includes CT endocranium, Doppler MKSC, TCD. In general, patients have fallen into delirious conditions that had been more or less successfully treated with haloperidol, risperidone and benzodiazepines. This has been standard for years in the world, and we have included the mandatory EEG procedure for these patients. There were 25 patients who were monitored, and indicated a clear epileptic activity mainly of FT or TO regions. We started with a small dose of lamotrigine, and a gradual introduction of it. First of all, in the context of delirious conditions, these are visible hallucinations and lamentations, crying and sometimes fear. After the introduction of antiepileptics, such symptoms have disappeared, gradually, with patient dosing and neurophysiological monitoring.
Recent Publications:
1. Refractory Epilepsy in Adults after CVI-published in the E Cronic 2017
2.Refractory status epileptics in adults after CVI, best poster award roma 2016.international conference on epilepsy and treatment
3. Ischemic stroke and migraine journal of neurological sciences 2013.
4. Stroke and leukoencephalopathy journal of neurological sciences 2013
5. Headche,migraine,brain lesion and MRI study journal of headache and pain 2013
Area of research interest : Cerebrovascular duseases,epilepsy, Non Convulsive status epllepticus, electrocenography,tarnslent ischmic attacks
Keynote Forum
Olivier Baledent
1University of Picardie Jules Verne, France
Keynote: CSF flows: from origins to alterations
Time : 12:05-12:50
Biography:
Olivier Balédent has completed his PhD in Biophysics and Radiology at Jules Verne University. He is currently working as an Assistant Professor at Amiens University Hospital in France. He is heading the Department of Medical Image Processing and Bio Flow Image research team. After Master’s degree in Informatics in Amiens, he completed a Postgraduate Diploma in the field of Image Processing in Lyon. The thesis subject was about CSF flow imaging using MRI technique. Now, at Amiens University Hospital, with clinicians, he continues to develop CSF research and applies non-invasive hydrodynamic approach in clinical practice. He is also a Biophysics Teacher at Medical School of University of Picardie Jules Verne.
Abstract:
The rapid amplitude change of the cerebral systolic arterial input flow increases the brain volume. Then cerebrospinal fluid (CSF) is quickly displaced out of the cranium toward the spinal canal; intracranial pressure (ICP) increase is therefore limited. Nevertheless, this first CSF response is also limited and has to be supplemented with the cerebral blood venous outflow. The venous contribution is slower than the CSF but at the end drains from the cranium all the blood input volume. Finally, due to the narrow aqueduct of Sylvius, a small CSF ventricular flows out of the fourth ventricle. Cerebral hydrodynamics knowledge has benefited considerably from the introduction of phase-contrast magnetic resonance imaging (PCMRI), the unique technique to investigate the small but rapid CSF oscillations. Using post-processing software, key parameters of flow can be easily calculated. In ten minutes CSF flow is quantified in the spinal subarachnoid spaces, the pontine cistern, the foramens of Magendie and the aqueduct of Sylvius. Blood flow is quantified in the internal carotid and the vertebral arteries, straight and sagittal sinus, jugular and epidural veins. These flows data can be functional information’s complementary to the morphological imaging to better investigate the cranio-spinal system in case of patients presented hydrocephalus, Chiari malformation, syringomyelia, cerebral hemorrhage, intracranial hyper or hypo tension. The objective of this presentation is to describe the power and the limit of such clinical 2D PCMRI protocol concerning CSF and blood flow investigations and present what we have found in different healthy and pathological populations.
- Neurology | Dementia | Child Neurology | Central Nervous System | Neurophysiology | Neuromuscular Disorders
Chair
Gjumrakch Aliev
University of Atlanta, USA
Co-Chair
Natasa Radojkovic Gligic
University of Belgrade, Serbia
Session Introduction
Zena Vexler
University California San Francisco, USA
Title: Neurovascular interface in stroke: effects of age
Biography:
Zena Vexle has served as Director of Research at Neonatal Brain Disorders Center, since 2003. She has served on the NIH study sections and chaired Brain 2 and Brain 3 Committees for American Heart Association.She has multi-disciplinary training in chemistry, biochemistry, pharmacology and physiology. For more than 25 years, her research has been centered on the mechanisms of experimental stroke, including cerebrovascular injury and neuro-inflammation.
Abstract:
The major barriers of the brain, the blood-brain barrier (BBB) and the blood-CSF barrier, tightly regulate the transport of molecules, cells and ions between the peripheral circulation and parenchyma. Barrier properties change during brain maturation and aging, affecting susceptibility to and the pathophysiology of various neurodegenerative diseases in age-related manner. Data are emerging that the phenotypic endothelial cell heterogeneity, the more elaborate capillary network in the adult, differences in regional responsiveness of the vessels, pericyte and astrocyte phenotypes and coverage, distinctly modify hemodynamic regulation and BBB integrity after arterial stroke in newborns, children and adults. We will discuss the role of leukocyte-microglial communications in modifying BBB integrity in experimental stroke in three age groups. In particular, we will demonstrate that BBB is strikingly more integrant after perinatal stroke than after adult stroke, in part due to age-dependent expression of extracellular matrix proteins and tight junction proteins. We will then discuss our findings that at least a subpopulation of microglial cells protects both BBB integrity and the neonatal brain based on adverse effects of depletion of microglial cells or inhibition of microglial TGFbeta1 signaling on neurovascular integrity in injured brain. We will also discuss how disruption of monocyte and neutrophil signaling affects BBB structure-functional responses in stroke induced in different age groups.
Marina Zueva
Moscow Helmholtz Research Institute of Eye Diseases, Russia
Title: Fractal optical stimulation to support the cognitive ability in aging and TBI
Biography:
Marina Zueva is a Professor of Pathophysiology. She has completed her Graduation at the Lomonosov Moscow State University; PhD, at Moscow Helmholtz Research Institute of Eye Diseases. Currently, she is the Head of the Division of Clinical Physiology of Vision at the Moscow Helmholtz Research Institute of Eye Diseases. She has published over 15 peer-reviewed full-length papers in English and presented near 70 topics at international conferences. Her research topics include “Clinical physiology and electrophysiology of vision, neurophysiology, age-related and neurodegenerative disorders of the visual system and the brain, neurocognitive technologies of the restoration, maintenance and improvement of the brain activity and cognitive functions”.
Abstract:
Cognitive decline is characteristic of various pathological conditions including traumatic brain injury (TBI) and can accompany normal aging. Technologies of neurorehabilitation exploiting the structural-functional plasticity of the brain could promote the forming of new connections to compensate the cognitive deficit. Methods of cognitive rehabilitation include techniques of mental and physical training and different regimens of stimulation therapy such as transcranial magnetic and electrical stimulation, and low-intensity stimulation by sensory stimuli, positive effects of which were shown in many studies. However, taking into account that in aging and pathology potential of neuroplasticity is reduced, the efficacy of any methods of neurorehabilitation can be objectively restricted. Besides, in the stimulation therapy, optical, audio and other signals with a regular, periodic temporal structure are usually applied. The periodic rhythms can provide some improvement of the cortical activity in the particular range of EEG. But they cannot restore complex fractal dynamics of the brain's activity typical of a healthy person and improve the cognitive ability of the patient. We suppose that the fractal stimulation by complex-structured optical signals and sound tones will promote activating the structural-functional plasticity and improve cognitive functions in pathological conditions associated with the cognitive decline. Evoked changes in the cortical activity can ensure the impact of stimulation on cognitive functions. Because the fractal stimulation is supposed to increase the potential of neuroplasticity, during the period of enhanced plasticity (against the backdrop of a course of stimulation therapy) an increase in the efficiency of different others neurorehabilitation measures should be expected.
Josef Finsterer
University of Veterinary Medicine Vienna, Austria
Title: Brain imaging in adult mitochondrial disorders
Biography:
Finsterer J. received his M.D. and Prof. of Neurology from the University of Vienna, Austria. Since his training as a clinical neurologist and electrophysiologist at the Neurological Krankenhaus Rosenhuegel and the Ludwig Boltzmann Institute for Epilepsy and Neuromuscular Disorders he is involved in the management of neuromuscular disorders, particularly muscular dystrophies and metabolic myopathies. In addition to neuromuscular disorders, research interests focus on genetics, orphan diseases, and cardiac involvement in genetic conditions.
Abstract:
Since the central-nervous-system (CNS) is the second most frequently affected organ in mitochondrial disorders (MIDs) and since MIDs are increasingly recognised, it is important to know about the morphological CNS abnormalities on imaging in these patients. The study aims at summarising and discussing current knowledge and recent advances concerning CNS imaging abnormalities in adult MIDs. The most relevant CNS abnormalities in adult MIDs on imaging include white and grey matter lesions, stroke-like lesions as the morphological equivalent of stroke-like episodes, cerebral atrophy, calcifications, optic atrophy, and lactacidosis. Since these CNS lesions may go along with or without clinical manifestations, it is important to screen all MID patients for cerebral involvement. Some of these lesions may remain unchanged for years whereas others may be dynamic, either in the sense of progression or regress. Typical dynamic lesions are stroke-like lesions and grey matter lesions. Clinically relevant imaging techniques for visualization of CNS abnormalities in MIDs are the computed tomography, magnetic-resonance-imaging, MR-spectroscopy, SPECT, PET, and angiography. CNS imaging in adult MIDs is important for diagnosing and monitoring CNS involvement. It also contributes to the understanding of the underlying pathomechanisms that lead to CNS involvement in MIDs.
Drini Dobi
Service of Neurovascular Disorders, University Hospital Center “Mother Teresaâ€, Tirana, ALBANIA
Title: ISCHEMIC CEREBROVASCULAR ACCIDENTS IN VERY OLD PERSONS
Biography:
Dr. Drini DOBI was born in January 27th, 1969, and graduated as PhD in University of Tirana, Albania in 1992, and has done the specialization course in Neurology from 1994-1998 in University Hospital Centre "Mother Teresa", Tirana Albania. After his specialization, he has done some other minispecialization course for neurorehabilitation in Instituto Carlo Besta, Milano, Italy, San Carlo , Milan, Italy and Don Carlo Gnocchi Milano, Italy and minispecialization course for neurosonology in UHC "Sestre Milosrdnice" Zagreb, Croatia. He has a lot of publications in some medical periodics and has participated in some of AAN Annual Meetings with his works, EFNS and EAN conferences, with his works too, and some other Neurological Conferences abroad. His Masters is in Rehabilitation in Parkinson Disease, in 2005 and PhD in Physical Rehabilitation after stroke in 2015. He is also the Member of EAN Scientific Pannel of Neurorehabilitation ,Scientific Pannel of neurotoxicology, and General Neurology
Abstract:
Statement of the Problem: Presently, there is limited information on stroke care in the very old (80 years and older). Population aging is a summary term to describe shifts in the age distribution of a population toward older ages, most marked in highly developed countries.The number of people aged 80 and above is growing faster than any other age group. In 2006, people aged 80 and over were approximately 19% of the population in developed countries and around 10% in developing countries. The purpose of this study is To evaluate vascular risk factors, stroke subtypes and clinical outcomes in very old patients admitted at our hospital with acute stroke.Methodology & Theoretical Orientation: We included in this study 252 stroke patients admitted to Service of Neurovascular Disorders in University Hospital Centre “Mother Teresa”, Tirana, Albania from February 2015 to December 2016. We assess if there were any significant differences between patients under 80 years old compared with older patients (80 years or older), with regard to vascular risk factors, stroke type and clinical outcome.Findings: Of 252 patients, 189 patients were less than 80 years, 63 were 80 years old and older.Younger patients were more likely to have diabetes (30, 6% versus 16, 2%, p<0,001).Older patients were more likely to have ischemic heart disease (38% versus 30, 1% p=0, 02), or atrial fibrillation (34, 5% versus 15, 2%, p<0,001).Older patients were more likely to have Total Anterior Circulation Infarcts (TACI) strokes (17, 6% versus 11, 1%, p<0,009) or Partial Anterior Circulation Infarct strokes (PACI) (30, 1% versus 23, 5%, p=0, 04)Outcome data, which was available for 91% patients, showed that older patients stayed longer in hospital (median length of stay 23 days versus 18 days, (p=0,008) and had a higher inpatient mortality 14% versus 3, 7%, (p<0,001).Conclusion & Significance: Very elderly patients have a different risk factor profile, have more anterior circulation infarcts and have a worse prognosis-with increased mortality and increased length of stay in hospital.
Muhammad Mahajnah
Hillel-Yaffe Medical Center, Israel
Title: The role of hypomorphic mutations in POLR3A in progressive sporadic and recessive spastic ataxia
Biography:
Muhammad Mahajnah is an Assistant Professor of Pediatrics and Pediatric Neurology at the Technion Faculty of Medicine, Israel. He completed his Medical degree at Bruce and Ruth Rappaport Faculty of Medicine, Technion, 31096 Haifa, Israel in 1992 and his PhD degree in 1998. He trained in Pediatrics at Carmel Medical Center and completed fellowship in Pediatric Neurology at Schneider Children Medical Center, Tel Aviv. He has worked with children neurological disorder for about 20 years and has special interest in neurodevelopmental disorders and neuro genetic disorders and devotes his time to both clinical work and research.
Abstract:
About half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. We screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n=618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in ∼3.1% of index cases. Interestingly, >80% of POLR3A mutation carriers presented the same deep-intronic mutation (c.1909+22G>A), which activates a cryptic splice site in a tissue and stage of development-specific manner and leads to a novel distinct phenotype. The phenotype is characterized by adolescent-onset progressive spastic ataxia with frequent occurrence of tremor, involvement of the central sensory tracts and dental problems (hypodontia, early onset of severe and aggressive periodontal disease). Instead of the typical hypomyelination magnetic resonance imaging pattern associated with classical POLR3A mutations, cases carrying c.1909+22G>A demonstrated hyperintensities along the superior cerebellar peduncles. These hyperintensities may represent the structural correlate to the cerebellar symptoms observed in these patients. We demonstrate that autosomal-recessive mutations in POLR3A are a frequent cause of hereditary spastic ataxias, accounting for about 3% of hitherto genetically unclassified autosomal recessive and sporadic cases; hypomyelination is frequently absent in POLR3A-related syndromes, especially when intronic mutations are present, and thus can no longer be considered as the unifying feature of POLR3A disease. Our results demonstrate that substantial progress in revealing the causes of Mendelian diseases can be made by exploring the non-coding sequences of the human genome.