Scientific Program

Day 1 :

Keynote Forum

Ailian Du

Shanghai Jiaotong University School of Medicine China

Keynote: Heteroplasmy of mtDNA 3243A>G mutation in seven Han Chinese families by pyrosequencing

Time : 10:00-10:40

Biography:

Vise director of Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine. She was graduated from Huashan Hospital, Fudan University and worked at Second Affiliated Hospital, Zhejiang University School of Medicine for 10 years. She has been studied at University of Califonia San Diego as Visiting Scholar for 2 years from 2008 to 2010. She is specialized in neuro-immune diseases and neuromuscular diseases and advanced on the research of myasthenia gravis and mitochondrial disease. Her publications including Autophagy(2017), J Immunol, (2013), Mitochondrion(2011) et al seven SCI publications and 20 Chinese publications.

Abstract:

To study the heteroplasmy and phenotype correlations of mtDNA 3243A>G mutation in 7 Han Chinese families using restrict fragment length polymorphism (RFLP) and pyrosequencing (Pyro). Methods Seven probands were pathologically and genetically diagnosed as mitochondrial diseases with 3243A>G mutation. The clinical phenotypes were studied in 39 maternal family members. 5 were diagnosed as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 2 with pure mitochondrial myopathy (MM), 1 with early neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome. Six with diabetes, 3 with hearing loss, and 20 family members are normal. Blood DNA from 37 members were detected with RFLP and pyrosequencing. mtDNA 3243A>G heterogeneity were analyzed. Results Mutation load in blood of 5 MELAS patients were 15.7% by RFLP (29% by Pyro), 12.8% (19% by Pyro), 40.1% (53% by Pyro), 25.8% (30% by Pyro), 28.3% (59% by Pyro). Mutation load in 2 MM patients were 13.7% (29% by Pyro) and 76.8% (79% by Pyro), and that in the NARP patient was 20.0% (57% by Pyro). Six family members with diabetes were range from 3.7%-7.6% (0%-14% by Pyro). Three family members with hearing loss were range from 4%-18.2% (6%-18%). The mutation load of 14 normal family members range from 2% to 12.5% (0%-5% by Pyro). Detection by Pyro is more accurate than RFLP when mutation load is lower than 10%. The mutation load is higher in those earlier age of onset. Conclusion Pyrosequencing is more reliable when mutation load is lower than 10%. The mutation load is negatively correlate to the age of onset in this research.

Keynote Forum

Umur Kayabasi

Bahcesehir University, Turkey

Keynote: Tau Protein in the Retina

Time : 10:40 - 11:20

Biography:

Umur Kayabasi is a graduate of Istanbul Medical Faculty. After working as a resident in Ophthalmology, he completed his clinical fellowship program of Neuroophthalmology and electrophysiology at Michigan State University in 1995. After working as a consultant neuro- ophthalmologist in Istanbul, he worked at Wills Eye Hospital for 3 months as an observer. He has been working at World Eye Hospital since 2000. He has chapters in different neuro- ophthalmology books, arranged international symposiums, attended TV programs to advertise the neuro- ophthalmology subspecialty. He has also given lectures at local and international meetings, plus published papers in neuro-ophthalmology. He became an assistant professor at Uskudar University- Istanbul in 2015.

Abstract:

Background: Recent research suggests that Tau is the culprit lesion along with neuroinflammation in the etiology of Alzheimer' s Disease ( AD ).  Retina is the extention of the brain and is the most easily approachable part of the central nervous system.  Detection of the pathological protein accumulations may be possible by using spectral domain optical coherescent tomography ( SD-OCT ) and fundus autofluorescein ( FAF ).  There is evidence showing that retinal plaques start accumulating even earlier than the ones in the brain.  Most recent Tau protein images in the brain consist of normal or reverse C-shaped paired hellical filaments. Methods: 20 patients with PET proven AD were examined by SD-OCT and FAF.  Mean age was 72. Hypo or hyperfluorescent retinal  lesions were scanned by SD-OCT and C shaped paired hellical filaments were investigated in a masked fashion.  The researchers agreed on the shape of the lesions. Both C-shaped ( normal or reverse ) filaments and thinner  fibrillary structures were taken into consideration. Results: In all the patients, paired hellical filaments that exactly corresponded with the histopathologic and cryo-EM images of Tau in terms of shape and dimension were detected along with thin fibrils and lesions similar to amyloid beta.  The number of the retinal filaments  and other abnormal proteins was in concordance with the severity of the disease process. The advanced retinal filaments had normal or reverse paired C shapes and thin fibrils had the shape of histopathologic images seen in early developmental stages of the disease. Conclusions: Retinal images of Tau were disclosed for the first time in live AD patients.  Retinal neuroimaging is a trustable biomarker and tool for monitoring the disease.

Keynote Forum

Diego Dolcetta

The Regina Elena National Cancer, Institute Italy

Keynote: A short treatment with intracerebroventricular mTOR inhibitors causes a complete and lasting cognitive recovery in an animal model of Alzheimer's disease

Time : 11:40 - 12:20

Biography:

Born in Venice, graduated in Padua, Neurologist (Pavia, 2001), Ph.D. in Neuroscience (Siena, 2005). During his studies he worked on gene therapy of lysosomal storage disorders at the Telethon Institute of Gene Therapy (TIGET) located in the San Raffaele Hospital in Milan. After a short experience in the stem cell research institute (SCRI) in the same hospital and after a serious car accident, in 2008 he moved to Vicenza (BIRD), where he undertook the study of other rare genetic diseases, such as the Lesch-Nyhan disease (he is the reference neurologist of the Italian Association of patients with LND since its foundation, in 2013). Since 2014 he works as a Guest Researcher at the laboratory of dr. Federico De Marco, of the IFO-IRE Institute, Rome.

Abstract:

Background: Rapamycin and other mTOR inhibitors have been shown to improve Alzheimer's disease, by acting in several key-points of pathogenesis. This has led to think of a central pathogenetic role of the mTOR hyperactivation. The inhibition of this kinase reduces both the synthesis of the precursors of beta-amyloid, and the accumulation of the latter, thanks to the activation of autophagy. This has a preventive effect, but especially therapeutic in already established disease, as long as initial. Recently Kurdi et al. showed that after a few days of mTOR inhibition, autophagy escapes the control of mTOR.We thought that a high dose for a few days was the best way to harness the therapeutic efficacy of rapalogs. Since rapalogs are not burdened by heavy neurological side effects, this dose can be achieved only locally, via intracerebroventricular infusion (icv). METHODS: In mice 3xTg-AD, an excellent animal model of AD, icv administration of a rapalog for 7 days in mice of 6 months of age, with an initial but measurable cognitive impairment. Results: The treatment produced a full restoration of cognition, with corresponding pathological evidences. The benefits lasted for about two months from administration. Mice were then sacrificed, so we do not know the exact duration of the therapeutic effect. Conclusions: We believe that this therapy, certainly invasive but very short and surprisingly effective, deserves to be tested on patients, as soon as the diagnosis is established.

Keynote Forum

Ying Peng

Sun Yat-Sen University China

Keynote: Diagnoses and treatments of chronic alcoholic toxic cerebral encephalopathy: an expert consensus Specialized Committee Professional Board of Brain and Spinal Cord Injury, Neurology Branch of Chinese Medical Doctor Association

Time : 12:20 - 13:00

Biography:

Ying Peng, M.D. & Ph.D. From 1997 to 2001, he got his post-doctor training in National Institutes of Health, USA. Now He is working in Sun Yaat-Sen Memorial Hospital, Sun Yat-Sen University as a full-professor.  His current research fields include: 1. Addiction & Toxic Encephalopathy; 2. Gene therapy of Neurological Disease; 3. Cerebral ischemic stroke; 4.Brain injure and neural regeneration. He got 7 funds during the period of working in the University of Hong Kong and 16 grants after working in the Sun Yat-Sen Memorial Hospital. He published 105 papers in SCI journals. Additionally, he got the “Fellows Award for Research Excellence 2001”, sponsored by National Institutes of  Health of  USA., and the “Second Prize for Scientific Technique Progress Award of Guangdong Province” in China.

Abstract:

Chronic alcoholism encephalopathy is a common disease existing all over the world, which is an important symptom of alcohol abuse and alcoholism. In order to promote neurologists’ understanding, popularize the standardized diagnosis and treatment of chronic alcoholism encephalopathy, we have made extensive discussion to reach the following consensus on the principles related to the clinical diagnosis and treatment on chronic alcoholism encephalopathy.I. Definition of chronic alcoholic encephalopathy : Chronic alcoholism encephalopathy is a chronic and recrudescent brain disease caused by alcohol acting on the brain tissue due to long-term drinking, that is to say, a seriously poisoning condition on the central nervous system caused by excessive drinking for a long time, and almost all patients have dependently chronic pathogenesis of alcohol syndrome. II. Clinical manifestations and characteristics of chronically alcoholic encephalopathy : We divide chronic alcoholism encephalopathy into 6 kinds of syndrome according to the patient's clinical manifestation and the condition of onset and the duration of the disease, including Wernicke encephalopathy, Coxsackoff syndrome, chronic alcoholism dementia, alcoholic tremor-delirium, alcoholic epilepsy, alcoholically mental and behavioral disorders.III. Clinical diagnosis of chronic alcoholic encephalopathy : The coring symptoms/diagnostic criteria for alcohol dependence are described in DSM-4/ICD-10 as followings (3 Or more of the following within 12 months): (1)Alcoholic tolerance;(2)interrupting symptoms/reactions after stopping drinking; (3)Excessive intake; (4)Beyond control and abstinence; (5)Spending a lot of time seeking, acquiring and ingesting alcohol; (6)The intention of social communication is decreased; (7)Regardless of any adverse consequences. The clinicians should be based on the above-mentioned diagnostic criteria, combined with the clinical manifestations and imaging characteristicsfor comprehensive judgment. IV. Treatment of chronically alcoholic encephalopathy : Abstinence from alcohol: Currently first-line medicine: Nalmefen, naloxone, dithiolam, aconic acid; The second-line medicine: Baclofen, topiramate, benzodiazepines, tricyclic antidepressants, high-dose antioxidants. Others include etiological treatment, correction on nutritional disorders, brain-protecting therapy, rehabilitation therapy and others.

  • Neurology

Session Introduction

Xiaoni Zhang

Sun Yat-Sen University China

Title: Substance Dependence Alters Serum Lipid Levels in Addicted Male Patients
Speaker
Biography:

Dr. Xiaoni Zhang has her expertise in clinical and mechanism studies of substance dependence. Dr. Zhang has completed her M.D. and M.S. at Sun Yat-Sen University. She is currently a resident at Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Her research field is focused on substance dependence and morphine-induced immunosuppressive effects.

Abstract:

Objectives: Studies have shown that opiate and heroin dependence causes alterations in serum lipids. In this study, we investigated the relationship between different types of substance dependence and serum lipid levels. Methods: Serum lipid levels were measured in 97 patients with different types of substance dependence (heroin, methamphetamine, ketamine, and codeine phosphate dependence), and in 99 healthy subjects. The clinical characteristics of substance-dependent patients were also investigated. Results: Serum total cholesterol (TC; 3.74±1.02 mmol/L, P=0.017) and high-density lipoprotein cholesterol (HDL-C; 1.12±0.19, P=0.007) levels were lower, and triglyceride levels (TG; 1.73±0.89 mmol/L, P=0.008) were higher in the heroin dependence group compared to the control group. Serum TG (1.74±1.11 mmol/L, P=0.000), HDL-C (1.44±0.30 mmol/L, P=0.011), apolipoprotein A-1 (ApoA-1; 1.55±0.28 g/L, P=0.000), and apolipoprotein B (ApoB; 1.55±0.28 g/L, P=0.000) levels were higher in the methamphetamine dependence group, while serum TG (2.49±1.56 mmol/L, P=0.000) and ApoB (0.93±0.25 g/L, P=0.000) levels were higher in the ketamine dependence group compared to the control group. Additionally, the codeine dependence group exhibited higher serum TG (1.94±1.34 mmol/L, P=0.000) and ApoB (0.82±0.28 g/L, P=0.003) levels. We also found that patients with psychotic symptoms had significantly higher TG levels in the heroin, methamphetamine, and ketamine dependence groups, and lower TC and HDL-C levels in the heroin dependence group.

Conclusions: Our data suggested that different types of substance dependence caused varying degrees of change in serum lipid levels, and that hypertriglyceridemia was consistent with psychotic symptoms in substance abuse patients.

Ailian Du

Shanghai Jiaotong University School of Medicine China

Title: Heteroplasmy of mtDNA 3243A G mutation in seven Han Chinese families by pyrosequencing
Speaker
Biography:

Ailian Du is the professor in Shanghai Jiotong University School of Medicine, China.

Abstract:

To study the heteroplasmy and phenotype correlations of mtDNA 3243A>G mutation in 7 Han Chinese families using restrict fragment length polymorphism (RFLP) and pyrosequencing (Pyro). Methods Seven probands were pathologically and genetically diagnosed as mitochondrial diseases with 3243A>G mutation. The clinical phenotypes were studied in 39 maternal family members. 5 were diagnosed as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 2 with pure mitochondrial myopathy (MM), 1 with early neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome. Six with diabetes, 3 with hearing loss, and 20 family members are normal. Blood DNA from 37 members were detected with RFLP and pyrosequencing. mtDNA 3243A>G heterogeneity were analyzed. Results Mutation load in blood of 5 MELAS patients were 15.7% by RFLP (29% by Pyro), 12.8% (19% by Pyro), 40.1% (53% by Pyro), 25.8% (30% by Pyro), 28.3% (59% by Pyro). Mutation load in 2 MM patients were 13.7% (29% by Pyro) and 76.8% (79% by Pyro), and that in the NARP patient was 20.0% (57% by Pyro). Six family members with diabetes were range from 3.7%-7.6% (0%-14% by Pyro). Three family members with hearing loss were range from 4%-18.2% (6%-18%). The mutation load of 14 normal family members range from 2% to 12.5% (0%-5% by Pyro). Detection by Pyro is more accurate than RFLP when mutation load is lower than 10%. The mutation load is higher in those earlier age of onset. Conclusion Pyrosequencing is more reliable when mutation load is lower than 10%. The mutation load is negatively correlate to the age of onset in this research.

Elham Ataei

Assistant University of Medical Sciences Iran

Title: Evaluation of Short-term Mortality of Status Epilepticus and Its Risk Factors
Speaker
Biography:

Elham Ataei is the Assistant of Neurology at  Rasool Akram Hospital, University of Medical Sciences Tehran, Iran.

Abstract:

Background and Purpose: Status epilepticus (SE) is defined as epileptic seizures of greater than five minutes or more than one seizure within a five minute period without returning to normal consciousness between them. It is a life-threatening condition particularly if treatment is delayed. Previous studies reported age, duration and etiology of SE as primary determinants of mortality. Methods: This prospective cross-sectional study performed on the patients with status epilepticus admitted in Rasoul-e-Akram hospital in Tehran. Patients followed at 30th day after SE to assess their living status. Results: Sixty-five patients, (56.9% was male) with 15 to 88 years of age entered the study. Mean duration of SE was 40 minutes and for hospital stay was 7 days. 84.6% of patients responded to treatment and 11 patients (16.9%) died within 30 days after SE. Mortality rate in patients with refractory SE was 70%. Mean interval between SE and death was 11.9 ± 11.7 days. Age, duration of SE and hospital stay, history of head trauma and neurosurgery were not predictors of mortality. Negative history for epilepsy had significantly higher mortality rate. Anoxic encephalopathy increased the mortality rate and response to treatment decreased it. Conclusions: Short-term mortality rate of SE was comparable with most of the previous reports Since our hospital has equipped emergency department, resuscitation and primary treatment of SE is usually start soon, percentage of anoxic encephalopathy is decreased and lower mortality rate is expected. We conclude that early treatment by decrease chance of anoxic encephalopathy, has significant role in outcome of SE. Keywords: Status epilepticus, Mortality rate, Refractory seizure.

  • Stroke and Dementia

Session Introduction

Noor-ul-huda Maria

Punjab Institute of Neurosciences,Pakistan

Title: Relation of Lipid Profile with ischemic Stroke
Speaker
Biography:

Dr.Noor ul Huda Maria is one of a few female neurosurgeons in Pakistan .She is currently working at Pakistan's largest dedicated neurosurgery hospital ,Punjab institute of neurosciences (PINS).She has completed her fellowship training from the same institute as well.Graduate of Services Institute of Medical Sciences with top position ,distinctions and gold medals, she has always been passionate about neurosurgery.She has got special interest in research work and has various articles published in national and international journals.She has presented her abstracts and e posters at different international conferences.Currently working on a book.

Abstract:

Objective: to evaluate correlation of blood total cholesterol (TC), high-density lipoprotein (HDL), triglycerides, and the TC:HDL ratio as risk factors for ischemic stroke. Methodology: After ethical approval from hospital ethical board this case control study was conducted in the department of neurosurgery and neurology Lahore General Hospital Lahore/Punjab Institute of Neurosciences/Postgraduate Medical Institute/Ameerudin Medical College Lahore. Duration of study was two years from October 2015 to October 2017. A total of 600 patients were included in the study after obtaining written consent from patients. After completion of data collection, data was entered in computer software SPSS version 23 and analyzed for continuous and categorical variables. Continuous/numerical variables were presented as mean and SD and categorical variables were presented in form of numbers and percentages. Independent t-test and chi-square test were applied to see significance of data. P value less than or equal to 0.05 was considered as significant. Results: Overall, 100% (n=600) patients were included in this study. The study comprised of two equal groups, 50% (n=300) in each, i.e. cases and controls. The  controls had mean TC, HDL and triglycerides 220.76±4.29 mg/dL, 54.02±4.45 mg/dL and 153.99±2.68 mg/dL respectively. The TC:HDL ratio was 5.48±1.41 and 4.09±1.22 for cases and controls respectively. The mean differences between TC, HDL, triglycerides and TC: HCL ratios were statistically significant among both groups. Conclusion: Results of our study revealed that significant difference was observed between cases and controls regarding the levels of Total cholesterol , HDL, triglycerides and TC:HDL ratio. Cases of ischemic stroke were found with high levels of TC, Tridlycerides, And TC:HDL ratio and low HDL , this difference was found statistically significant with P value 0.001. so it was concluded that hyperlipidemia has significant relation with ischemic stroke.

  • Young Research Forum

Session Introduction

Bence Andras Lazar

Bence Andras Lazar, University of Szeged, Hungary

Title: Neurochemical Characterization of Insulin Receptor Expressing Primary Sensory Neurons in the Rat
Speaker
Biography:

Bence Andras Lazar is working as a Ph.D. candidate in the Department of Physiology, University of Szeged and as a clinical doctor in the Department of Psychiatry, University of Szeged. His current research fields include: neuromorphology and addictology. Now he is working with a fellowship of the UNKP-17-3 New National Excellence Program of the Ministry if Human Capacities.

Abstract:

Recent studies have revealed that insulin modulates the activation of the nociceptor specific, transient receptor potential vanilloid type 1 receptor (TRPV1) expressed on cultured rat primary sensory neurons (PSNs). It has also been demonstrated that insulin receptor (InsR) shows colocalization with TRPV1 in PSNs of unidentified target innervation territories. The aim of our current study was to reveal the neurochemical properties of identified somato- and viscerosensitive PSNs. In our first experiments, we assessed the localization of the InsR and its colocalization with the TRPV1 in spinal PSNs retrogradely labeled with biotin-conjugated wheat germ agglutinin (bWGA) injected into the dorsal hind paw skin, the gastrocnemius muscle, the pancreas and the urinary bladder wall. We also analyzed InsR, TRPV1, substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivities in retrogradely labeled pancreatic spinal and nodose ganglion neurons. We found that ~50% of visceral and ~20% of somatic PSNs showed InsR-immunopositivity. A major population of bWGA-labeled spinal and vagal PSNs exhibited TRPV1 immunoreactivity. Our results also showed that ~15% of somatic and ~30% of visceral spinal PSNs displayed InsR and TRPV1 colocalization. Additionally, colocalization of the InsR with  SP or CGRP was demonstrated in 14% and 28% of pancreatic spinal and 24% and 8% of pancreatic vagal neurons. Our immunohistochemical data provide evidence for the colocalization of the InsR and the TRPV1 in somatic and visceral PSNs and demonstrate that a higher proportion of visceral PSNs express the InsR and display InsR-TRPV1 colocalization. Furthermore, our findings show that a relatively high proportion of pancreatic spinal and vagal PSNs display colocalization of the TRPV1, the InsR and sensory neuropeptides. We suggest that insulin may modulate TRPV1 activation and subsequent peptide release from visceral afferents and contribute to inflammatory and nociceptive mechanisms of the viscera.Keywords: insulin receptor; transient receptor potential vanilloid type 1 receptor; neuropeptides; primary sensory neurons; retrograde labelling; somatic and visceral organs; pancreas. Funding:. This work is supported by the GINOP-2.3.2-15-2016-00034 projects of the Hungarian National Research, Development and Innovation Office. B. A. Lázár is supported by the UNKP-17-3 New National Excellence Program of the Ministry of Human Capacities and TÁMOP 4.2.2.A-11/1/KONV-2012-0052

Day 2 :

Keynote Forum

Ailian Du

Shanghai Jiaotong University School of Medicine China

Keynote: Heteroplasmy of mtDNA 3243A>G mutation in seven Han Chinese families by pyrosequencing

Time : 10:00-10:40

Biography:

Vise director of Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine. She was graduated from Huashan Hospital, Fudan University and worked at Second Affiliated Hospital, Zhejiang University School of Medicine for 10 years. She has been studied at University of Califonia San Diego as Visiting Scholar for 2 years from 2008 to 2010. She is specialized in neuro-immune diseases and neuromuscular diseases and advanced on the research of myasthenia gravis and mitochondrial disease. Her publications including Autophagy(2017), J Immunol, (2013), Mitochondrion(2011) et al seven SCI publications and 20 Chinese publications.

Abstract:

To study the heteroplasmy and phenotype correlations of mtDNA 3243A>G mutation in 7 Han Chinese families using restrict fragment length polymorphism (RFLP) and pyrosequencing (Pyro). Methods Seven probands were pathologically and genetically diagnosed as mitochondrial diseases with 3243A>G mutation. The clinical phenotypes were studied in 39 maternal family members. 5 were diagnosed as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 2 with pure mitochondrial myopathy (MM), 1 with early neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome. Six with diabetes, 3 with hearing loss, and 20 family members are normal. Blood DNA from 37 members were detected with RFLP and pyrosequencing. mtDNA 3243A>G heterogeneity were analyzed. Results Mutation load in blood of 5 MELAS patients were 15.7% by RFLP (29% by Pyro), 12.8% (19% by Pyro), 40.1% (53% by Pyro), 25.8% (30% by Pyro), 28.3% (59% by Pyro). Mutation load in 2 MM patients were 13.7% (29% by Pyro) and 76.8% (79% by Pyro), and that in the NARP patient was 20.0% (57% by Pyro). Six family members with diabetes were range from 3.7%-7.6% (0%-14% by Pyro). Three family members with hearing loss were range from 4%-18.2% (6%-18%). The mutation load of 14 normal family members range from 2% to 12.5% (0%-5% by Pyro). Detection by Pyro is more accurate than RFLP when mutation load is lower than 10%. The mutation load is higher in those earlier age of onset. Conclusion Pyrosequencing is more reliable when mutation load is lower than 10%. The mutation load is negatively correlate to the age of onset in this research.