26^th European Neurology Congress August 06-08, 2018 Madrid, Spain

Myung Koo Lee, Professor of College of Pharmacy, Chungbuk National University (CNU), Korea, has completed his Ph.D. from the Faculty of Pharmaceutical Sciences, Kyushu University (Japan) in 1988 and postdoctoral studies from Cornell University Medical School in 1991-1992. He has served as a dean at the College of Pharmacy, CNU in 2002-2004, and as a president at the Society of Korean College of Clinical Pharmacy in 2010-2012. He has also served as the director at the Research Center for Bioresource and Health, CNU in 2001-present. He has published more than 210 papers in journals.

 

Parkinson’s disease (PD) is caused by the degeneration of dopaminergic neurons in the substantia nigra-striatal region. L-3,4-dihydroxyphenylalanine (L-DOPA) is the most frequently prescribed drug for controlling the symptoms of PD. However, the high levels of L-DOPA lead to cell death by generating reactive oxygen species in dopaminergic neuronal and PC12 cells. Recently, it has been reported that the intracellular cyclic AMP levels increased in response to cytotoxic levels of L-DOPA and multiple treatments with non-toxic L-DOPA (MT-LD) reduced dopamine biosynthesis in PC12 cells. In this study, the effects of L-DOPA on dopaminergic neuronal cell death via the ERK1/2 and JNK1/2-c-Jun systems were investigated. In PC12 cells, MT-LD (20 μM) induced cell survival via PKA-transient ERK1/2 activation, and then it induced differentiation via the Epac-sustained ERK1/2 system. MT-LD initially enhanced c-Jun phosphorylation (Ser73), but later induced c-Jun phosphorylation (Ser63) and c-Jun expression, which subsequently led to the cell death process. In the 6-hydroxydopaminelesioned rat model of PD (6-OHDA lesion), L-DOPA administration (10 mg/kg) protected against neurotoxicity through c-Jun phosphorylation (Ser73) for 1–2 weeks. However, L-DOPA administration (10 or 30 mg/kg) showed neurotoxicity through c-Jun phosphorylation (Ser63) and c-Jun expression via ERK1/2 phosphorylation for 3–4 weeks. In addition, gynosaponin TN-2 from ethanol extract of G. pentaphyllum (GP-EX) protected against L-DOPA-induced neurotoxicity in PC12 cells. Gypenosides and GP-EX also showed the protective effects on long-term L-DOPA administration in 6-OHDA lesion. Our data indicate that chronic treatment of L-DOPA causes neurotoxicity via the cyclic AMP-ERK1/2-c-Jun system in dopaminergic neuronal cells and GP-EX might serve as an adjuvant agent for PD.

 

 

 

Sophie Hu is a MD/MSc candidate completing her MSc in Community Health Sciences. Her research focuses on predicting dementia using emotional and behavioral indicators. She completed her Bachelor of Health Sciences in 2017. Her interests lie in improving patient health through clinical research and global health initiatives. In the local community, she has fundraised over $70 000 for mental health programs. In the global community, she has led hypertension and neuroscience projects in the Dominican Republic and China. She is excited to continue clinical and global health research and would like to begin a biotechnology startup in her career.

Introduction: Dementia is one of the most common neurological disorders globally with cases expected to double by 2031 in Canada alone. Although memory loss is a hallmark symptom, neuropsychiatric symptoms such as anxiety and agitation are early markers. Mild behavioral impairment (MBI) is an at-risk state for dementia characterized by sustained neuropsychiatric symptoms. We developed the MBI checklist (MBI-C) to assess motivation, mood, impulse control, social appropriateness and perception in pre-dementia patients.

 

Methods: Th e MBI-C has been administered in the cognitive neuroscience clinic at the University of Calgary, Canada (n=227). We analyzed baseline MBI-C and gold standard neuropsychiatric inventory questionnaire (NPI-Q) scores in relation to MoCA scores in normal cognition (n=38), mild cognitive impairment (n=93) and dementia (n=74) patients using linear regression.

 

Results: With increasing severity of cognitive diagnosis, neuropsychiatric symptoms worsen (MBI-C and NPI-Q scores increase) and cognition declines (MoCA score decreases). Th ose with worsened cognition tend to be older, female and have less education. We found for every one point increase in MBI-C score, there is a 0.082 point decrease in MoCA score (p=0.007). For every one point increase in NPI-Q score, there is a 0.192 point decrease in MoCA score (p=0.006). There is no modification but age and education are confounders.

 

Conclusion: Given that the MBI-C is more sensitive in detecting neuropsychiatric symptoms in pre-dementia populations, there is a shallower point change in MoCA score. Th e MBI-C may be used to detect neuropsychiatric symptoms in normal cognition and MCI patients. Both cognitive and behavioral scales should be used to assess neuropsychiatric symptoms and cognitive decline in patients.

Meryem Alagöz completed her BSc studies in Medical Biology at CerrahpaÅŸa Medical School, and pursued her MSc studies in Molecular Biology and Genetic Engineering at University of Sussex. She attained her PhD from University of Sussex. Her PhD Project involved in the investigation of genetic alterations in human breast and ovarian cancer. She had worked as a Post-doctoral research fellow at Kings College and Imperial College. She worked at University of Sussex for 7 years as a research fellow and still collaborating with them for her research. She has been investigating the molecular mechanisms involved in the development of human diseases such as cancer and brain disorders. She has been working as an assistant professor at Molecular Biology and Genetics Department of Biruni University since February 2017. She has been setting up the researh and diagnostic laboratories at the Genome Centre employing advances technologies such as Next generation sequencing. In near future, she would like to focus on DNA damage and repair fi eld where she gained extensive experience during her studies and research. She will employ these experiences to research into broader area of genetic disorders.

Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders, characterized by disruptions in social interactions, communication and limitations in behaviour. Early diagnosis is an important step to prevent progression of ASD. Recent developments in genetic technology provide useful tools to investigate molecular mechanisms involved in autism. Despite a number of noteworthy studies, there is not yet enough understanding of the genetic aetiology of ASD. Research should focus on multidisciplinary approaches to improve early diagnosis and intervention of autism. It is important to study combinatorial effects of genetic, epigenetic, environmental factors. Current research in ASD highlights the importance of identifying new approaches such as next generation sequencing (NGS) and microRNA (miRNA) technologies to develop new biomarkers and drugs. Our study focus on identify common gene variation in ASD patients and also novel

genes for early diagnosis using NGS.

Özgür AltınbaÅŸ has a MD degree in cardiovascular surgery and PhD student in biochemistry. He graduated from Justice Vocational School and International Rotary Foundation. He has studies in different fields of cardiovascular surgery and interested in molecular and biochemical pathways of the diseases. He is the member of varied vocational and charity organizations.

Stroke is the third most common cause of death all over the world after ischemic heart disease and cancer. Approximately 30% of the patients die within the first year of having a stroke and another 50% are left disabled (1). Atherosclerotic disease at the carotid bifucation has been shown to be responsable for greater than 20% to 25% of all strokes (2). A clear separation

between symptomatic and asymptomatic carotid artery stenosis is critical. If the patient has transient or permanent focal neurologic symptoms related to the ipsilateral retina or the cerebral hemisphere, is considered to be symptomatic (3). Carotid endarterectomy should be strongly considered for symptomatic patients with 70% to 99% stenosis and should also be considered for symptomatic patients with 50% to 69% stenosis if no other etiologic basis for the ischemic symptoms can be found. Surgery should be recommended only in selected patients with asymptomatic carotid artery stenosis because of the marginal benefit from revascularization in this patient population (4). Prompt evaluation and triage of patients with symptomatic carotid artery stenosis are essential to minimize the risk of early recurrent cerebrovascular events (5). In conclusion, symptomatic carotid artrey syndromes need urgent carotid duplex, MRI or DSA evaluation to determine the need for urgent surgery. Those with

the greatest degree of stenosis derive the greatest benefit from timely carotid endarterectomy.

 

Recent Publications : 

1. Louridas G, Junaid A. Management of carotid artery stenosis. Can Fam Physician 2005; 10(7): 984-989

 

2. Mintz BL, Hobson RW. Diagnosis and treatment of carotid artrey stenosis. JAOA 2000; 100(11): 22-26

 

3. Lanzino G, Rabinstein AA, Brown RD. Treatment of carotid artrey stenosis: Medical therapy, surgery, or stenting? Mayo Clin Proc 2009; 84(4): 362-368

 

4. Hobson RW et al. Management of atherosclerotic carotid artery disease: Clinical practice guidelines of the Society for Vascular Surgery. Journal of vascular surgery 2008; 48(2): 480-486

 

5. Rothwell PM, Giles MF, Chandratheva A, et al. Early use of Existing Preventive Strategies for Stroke (EXPRESS) study Eff ect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): A prospective population-based sequential comparison. Lancet 2007; 370(9596):1432-1442.

Avathvadi Venkatesan Srinivasan, driven by his quest for excellence joined Madras Medical College (MMC) and received MD (General Medicine) in 1978. Later he pursued and received DM in Neurology from his alma mater. His thirst for research, skills and the latest development in Neurology made him find his way to the National Institute of Neurology and Neurosurgery, his pioneering research work on Neuroleptic Malignant Syndrome got him bestowed with the PhD degree in 2002. It made him the fi rst ever recipient in Neurology from the Tamil Nadu Dr. M.G.R. Medical University, since its inception in 1988. His path breaking research (6 papers) in phantom limbs, stroke etc., with Padma Bhusan Dr. V S Ramachandran, Director, Center of Brain and Cognition, University of San Diego remain acclamatory to his undisputed authority in Behavioral Neurology and Movement disorders. He authored more than 100 scientific papers; dozens of his other work have found places in reputed medical journals and has published 12 chapters. His research papers presented, won acclaims in 60 national conferences and in 25 international conferences held in UK, USA, Japan, Australia, China, Europe and other countries. He is the only one from India to collaborate with Dr. V S Ramachandran, who is the first recipient of Padma Bhusan for his contribution to Neurosciences.

Kipps C M, et al. (2005) reported that movement disorders (MD) encompass disorders characterized by involuntary movements and/or loss of control or efficiency in voluntary movement. Fahn & Frucht (2002) defined movement disorder emergency (MDE) as any neurological disorder evolving acutely or sub-acutely, in which the clinical presentation is dominated by a primary movement disorder, and in which failure to accurately diagnose and manage the patient may result in signifi cant morbidity or even mortality. Based on this definition, MD emergencies are classified into six main divisions, which are: 1. Emergencies in Parkinson’s disease (PD): a. Parkinsonism-hyperpyrexia and dyskinesia-hyperpy rexia syndromes, b. acute parkinsonism, c. acute psychosis in Parkinson’s disease and, d. encephalitis lethargica; 2. Acute drug reactions: a. acute dystonia, b. neuroleptic malignant syndrome, c. serotonergic syndrome and, d. malignant hyperthermia; 3. Acute exacerbation of chronic MDs: a. status dystonicus, b. laryngeal dystonia in multiple system atrophy and other conditions, c. tic status and neurological complications of tics, d. Wilson’s disease emergencies, e. hypocalcemia, f. tetanus, g. strychnine toxicity and, h. rabies; 4. Acute chorea and hemiballism – hemichorea; 5. Stiff -person syndrome and; 6. Lethal catatonia. In this review, we covered situations in which the main manifestations are MDs that pose signifi cant risks for acute morbidity and mortality. Emergencies in MDs are not uncommon and they generally start insidiously and have slow progression. Neurophyscian generally diagnose and treat to prevent the acute and chronic complications in the intensive care units. Significant mortality and morbidity may be prevented if identified at the early hours and appropriate treatment started. In this workshop authors highlight the clinical conundrum of neuroleptic malignant syndrome. Doctoral thesis of this work has created a new AVS-CUV criterion of NMS which has been added to the world literature.

 

Tomas Budrys is a Radiologist working in the University Hospital at the Department of Radiology specializing in Nuclear Medicine and Neuroradiology. He is specialized in Nuclear Medicine and Neuroradiology. Tomas Budrys is a last year Doctoral student working as a Lecturer for more than three years, teaching students and residents. He has published three articles with Clarivate Analytics indexing. Currently, he is developing new radiology journal and maintaining many websites associated with radiology.

Tomas Budrys research interests include medical physics, neuroradiology, nuclear medicine and safety in radiology. He is also a Member of the organizations like RSNA (Radiological Society of North America), ESR (European Society of Radiology) and LRA (Lithuanian Radiology Association).

Aim & Introduction: Successful surgical ablation depends on accurate localization of the epileptogenic cortex. This is important both to ensure a complete resection of the epileptogenic focus and to reduce the resection volume as much as possible, limiting any potential neurocognitive deficits. To this end, patients typically undergo an intensive and extensive preoperative evaluation in combination with anatomical and functional imaging. We compared the amount of epileptogenic foci, determine most common localizations of epilepsy focal points in both functional and structural imaging methods and determined the success rate of surgery in the operated patients when the focal points of epilepsy coincided in all three imaging methods.

 

Methods: Fourteen patients underwent neurosurgical operation with removal of epileptogenic foci. Assessment of normality was verified by the Kolmogorov-Smirnov and Shapiro-Wilk tests. The Wilcoxon Signal Criteria were used to compare the two dependent samples whose data did not match the normal distribution. Concordance was evaluated by using Cohen's kappa (κ).

 

Results: Ten out of fourteen patients underwent surgery and demonstrated excellent postsurgical outcomes, with no epileptic seizures one year or more aft er the operation; 3/14 patients had 1-2 seizures aft er surgery and one patient had same or more epileptic seizures in duration of one year or more. Most common localization for epileptogenic activity in all three methods was temporal lobe (39.6-48.6%).

 

Conclusion: Surgical treatment may offer high hope for patients with intractable epileptic seizures. PET/CT are extremely useful imaging method to assist in the localization of epileptogenic zones. The dynamic functional information that brain PET/ CT provide is highly complementary to anatomical imaging in MRI and functional information in EEG.

 

Xueyan Jiang is doing her PhD study in Germany Center for Neurodegenerative Disease, DZNE. She fi nished her bachelor degree in Applied Mathematics and master degree in Psychology. She has published 3 papers in reputed journals (e.g. Human Brain Mapping).

Goal of this study was to investigate the structural and functional changes in the cerebellum in sporadic ataxia with adult onset (SAOA), and to test for potential associations between structural-functional alterations in the cerebellum and disease duration. 37 SAOA patients (62.38 ± 9.53years) and 49 healthy controls (HC) (65.08 ± 6.85years) underwent a structural and resting state functional MR (rs-fMRI) scan. Focusing on the cerebellum, we performed voxel-based-morphometry and a voxel-wised degree centrality (DC) as key marker for network integrity. Group differences were calculated using two-sample t-tests, controlling for age, gender and total intracranial volume (only structure) (p < 0.01; FWE corrected, cluster-extent 20 voxels). GM atrophy in both anterior (lobule I-IV) and posterior cerebellum (lobule VI, VIII, IX and X) and GMV alternations are highly related to clinical assessments in SAOA patients. Meanwhile, SAOA patients showed significant higher DC in the right and vermis VIII. Interestingly, the disease-related atrophy regions tend to be poorly connected in cerebellar networks. In general, regions found are known to be involved in motor and somatosensory processing, being in line with clinical appearance of SAOA.

 

Su Jin Noh has her expertise in drug development and evaluation in neurological disorders. She studied potential drug development by mechanism-based targeting for curing neurodegenerative disease such as Alzheimer’s disease, Parkinson’s disease and stroke during her PhD program. Now she focuses on discovery of pathology of neuropsychiatric disease including schizophrenia or addiction.

Accumulating evidence suggest that disrupted-in-schizophrenia 1 (DISC1) modulates dopamine mediated function and involved in gene transcription in the brain. Our study was focused on these novel functions of DISC1 in the dopamine system. We demonstrated that DISC1-deficient mice showed an increase in dopamine D1 receptor (DRD1) transcripts in striatal region of the brain. DISC1-deficiency resulted in facilitation of the psychostimulant effect of cocaine in DISC1-deficient mice. The dopamine 1 antagonist, SCH-23390 blocked the psychostimulant effect of cocaine in DISC1-deficient mice. To elucidate molecular mechanism of this phenomenon, we characterized a novel co-repressor complex for DRD1 gene locus composed of DRRF-mSin3A-DISC1. First, we could find a novel interaction between DISC1 and DRRF mainly co-localized in the nucleus. We also identified mSin3A binding with DRRF and DISC1, interestingly the binding intensity between DRRF and mSin3A was signifi cantly increased by DISC1 co-expression. Furthermore, we observed an altered dopamine receptor mediated signaling in cultured striatal neurons (DIV 7) from DISC1-deficient mice. The basal level of cAMP and p-ERK were remarkably increased in DISC1 mutant mice. Taken together, we demonstrate a role of DISC1 in the striatum during cocaine sensitization, suggesting distinct mechanism of DISC1 in modulation of dopamine system through DRRF-mSinA-DISC1 corepressor complex for DRD1 gene.