Name: Neuromuscular diseases 2017
Start: 2017-07-24
End: 2017-07-26
Location: Italy

Scientific Program

Day 1 : 2017-07-24

Keynote Forum

Session Introduction

Rekha Patel has her expertise in the area of PKR regulated cell apoptosis in response to cellular stress. Her research on biochemical and molecular pathways that regulate cellular survival after stress signals has been central to understanding the etiology of dystonia 16 . She has built this model after years of experience in research on PKR regulated signaling pathways. Her work has provided a groundwork to understand the common pathways that are dysfunctional in various forms of dystonias. Her pioneering work has offered a novel paradigm for more investigations in basic molecular pathways in dystonias and also for therapeutic interventions that may work for different dystonias.

Abstract:

Dystonia is an inherited neuromuscular movement disorder that can result from mutations in more than 25 different genes. The patients suffer from inability to control their dystonic, often sustained repetitive movements, and have a compromised posture. One type of primary dystonia, the early onset dystonia 16 (DYT16), has been shown to be result from various mutations in the PACT (also known as PRKRA) gene that has been well characterized for its role in regulating apoptosis in response to cellular stress.

Under conditions of viral, oxidative, or endoplasmic reticulum stress, the cellular apoptosis has been shown to be regulated by prolonged translation inhibition resulting from kinase activity targeting the eukaryotic translation initiation factor 2 alpha. Events leading to eIF2 alpha phosphorylation in response to cell stress are attributed to interactions between three double stranded RNA binding proteins: PACT, TRBP, and PKR. These proteins interact with each other forming homo- and heterodimers to impact cellular fate in response to stress signals. PACT is a protein activator of PKR, a serine-threonine kinase involved in innate immunity. PACT-PKR interaction is essential for facilitating apoptosis; whereas, transactivation RNA binding protein (TRBP) serves as a PKR inhibitor via PACT-TRBP and TRBP-PKR heterodimerization. We investigated the altered protein-protein interactions between PACT, PKR, and TRBP resulting from various mutations in DYT16 patients, and for the first time in a mouse model of DYT16. Using various biochemical techniques, we characterized how these mutations influence PACT’s function during stress response to regulate apoptosis. By utilizing DYT16 patient samples as well as an analogous mouse model with dystonia we are attempting to better understand how PACT mutations may lead to early onset dystonia. Our research highlights the insight obtained by applying biochemical, and molecular analysis to patient cells and mouse models to understand the etiology and pathophysiology of dystonia.

Luca Mesin

Polytechnic University of Turin, Italy

Title: Reduction of crosstalk in surface electromyogram by optimal spatio-temporal filtering

Biography:

Luca Mesin has done his Master’s degree in Electronics Engineering in 1999, PhD in Applied Mathematics in 2003. He is an Associate Professor in Biomedical Engineering at Polytechnic University of Turin, Italy. He is the Head of the research group on Mathematical Biology and Physiology. His research activities are devoted to the processing of signals or images extracted from biological and physiological systems and to the development of mathematical models for the interpretation of the recorded data. Applications are mainly focused on the investigation of biological systems or on the development of new biomedical tools. Recent works concern the simulation of spiral waves using a model of electromechanical coupling in the heart, the investigation of the central venous pressure, the processing of multiple data reflecting the responses of the autonomous nervous system and the simulation and processing of bioelectric signals.

Abstract:

Crosstalk can pose limitations in the applications of surface electromyogram (EMG). Its reduction can help in the identification of the activity of specific muscles. The selectivity of different spatial filters was tested in the literature both in simulations and experiments, but their performances are affected by many factors (e.g., anatomy and dimension/location of the electrodes). Moreover, they reduce crosstalk by decreasing the detection volume, recording data that represent only the activity of a small portion of the muscle of interest. In this study we propose an adaptive approach, which filters both in time and among different channels, providing a signal that maximally preserves the energy of the EMG of interest and discards that of nearby muscles (increasing the signal to crosstalk ratio, SCR). Tests with simulations and experimental data show an average increase of the SCR of about 2 dB with respect to the SD or DD data processed by the filters. The method is applied to few signals, proving its potential in applicative studies (e.g., clinics, gate analysis, and prosthesis control) where a limited number of non-selective channels are used.

Mohammad Wasay

The Aga Khan University, Karachi, Pakistan

Title: Arbovirus infections of nervous system â€“ trends and threats

Biography:

Abstract:

Arthropod-borne viruses (arboviruses) are among the most important international infectious threat to human nervous system. The neurological diseases that may be transmitted to humans in the traditional way by arthropods include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis (including anterior horn cells and dorsal root ganglia), and myositis. Arboviruses are distributed worldwide. However, different species have predilection for different geographical areas. Arboviruses are transmitted among vertebral hosts by blood feeding arthropod vectors including mosquitoes, biting flies, mites, nits and ticks. Some of the well-known encephalitides include West Nile encephalitis (WNE), Dengue fever encephalitis (DFE), St. Louis encephalitis (SLE), Japanese encephalitis (JE), Toscana encephalitis (TOE), Crimean-Congo hemorrhagic fever (CCHF), Chickeungunya virus encephalitis (CHIKV), Eastern equine encephalitis (EEE), and Western equine encephalitis (WEE). The keys to prevention of arboviral encephalitis include reduction of vector prevalence, reduction of amplifying of host susceptibility, avoidance of vector and reduction in human susceptibility through the use of insect repellants or immunization. With the widespread resistance to chemical control of vectors, novel methods like genetic control of vector populations are becoming increasingly important. The case fatality rate can range from <1% for LCE to as high as 70% in EEE. The case fatality rate for JEE and SLE is up to 30%. Neurological sequelae of arboviruses can result in permanent disability in as high as 90% of affected individuals depending on the virulence and type of the virus.

Table 1. Common arboviruses with their geographical distribution and vectors

Family	Virus	Vector	Geographical Distribution
Togaviridae
	Eastern Equine Encepahlitis Virus	Mosquito (Culiseta, Aedes)	Eastern and Gulf coasts of USA, Carribean islands, Central America and northeast coast of South America
	Western Equine Encephalitis Virus	Mosquito (Culiseta, Culex)	Midwest and Western USA, Canada
	Venezuelan Equine Encephalitis Virus	Mosquito (Aedes, Culex)	South and Central America, Southeast and Southwest of USA
	Chikungunya Virus	Mosquito (Aedes)	Africa, India, Southeast Asia
Flaviviridae
	St. Louis Encephalitis Virus	Mosquito (Culex)	North America, Central America and South America
	Japanese Encephalitis Virus	Mosquito (Culex)	Japan, Northeast Asia, Southeast Asia, Central Asia and Indian Subcontinent
	West Nile virus	Mosquito (Culex)	Africa, Mediterranean region, central Asia, India, Europe, North America, Central and South America
	Dengue Fever Virus	Mosquito (Aedes)	Asia, tropical and subtropical regions of the world
	Murray Valley Encephalitis Virus	Mosquito (Culex, Aedes)	Australia, New Zealand, New Guinea
Bunyaviridae
	California Encephalitis Virus	Mosquito (Aedes)	Western USA
	La Crosse Encephalitis Virus	Mosquito (Aedes)	Midwest and eastern USA
	Toscana Encephalitis Virus	Sand fly (Phlebotomus)	Europe, North Africa
	Rift Valley Fever Virus	Mosquito (Culex, Aedes and others)	East Africa, South Africa Nile valley, Saudi Arabian peninsula
	Crimean-Congo Hemorrhagic Fever Virus (Nairovirus)	Ticks (Hyalloma, Ixodid)	Africa, Europe, Asia
Reoviridae
	Colorado Tick Fever Virus	Ticks (Dermacentor)	Rocky mountains of USA

Zhen-huan LIU

Nanhai Hospital for Women and Children, P.R.China

Title: A randomized controlled study and Evaluation of Children with Cerebral Palsy by Mind Acupuncture

Biography:

Professor LIU ZHEN-HUANï¼Œis the deputy manager of the Affiliated Maternity and Child Care Hospital of Guangzhou University of Chinese Medicine. The director of the Rehabilitation Child of hospital, and the Doctoral tutor of the Guangzhou University of Chinese Medicine. Prof. Liu became one of the paediatricians who received the special state Council allowance in China in 1994, was given the title of the prominent contribute youth expert by the Healthy Ministry of China in 2002, Prof. Liu got the honour of “model worker in nationwide”. In addition, Prof. Liu is also the adjunct professor of The Chinese university of Hong Kong and Pharmacy and the Health Institute of Indonesian Ministry of Health. Professor Liu is famous Pediatric Neurology /Acupuncture Doctor in The world

Prof. Liu has the experience of more than 30 years specializing in TCM- Western pediatrics studies and 20 years in rehabilitation for cerebral palsy. He founded the Rehabilitation Centre for Cerebral Palsy of the Affiliated Maternity and Child Care Hospital of Guangzhou University of Traditional Chinese Medicineï¼Œwhich is one of the world's renowned medical department. Since foundation, it has received more than 30,000 children with mental retardation and cerebral palsy from many countries, including China, the United States, Japan, the United Kingdom, New Zealand, Singapore, Poland, etc. Prof. Liu has also actively involved in the academic field. Since 1993, he has been giving seminars and academic exchange programs with world renowned scholars from Oxford University, Cambridge University, in the field of the application and assessment of the application of acupuncture treatment for brain and cerebral palsy rehabilitation in children throughout the world such as The United States, the United Kingdom, Spain, Australia, Norway, and so on.

Abstract:

To investigate the effects of clearing the mind Acupuncture in neural development and remediation of children with cerebral palsy. Methods: 200 cases of children with cerebral palsy were randomly divided into the treatment group (n = 100) and the control group (n = 100). The treatment group was given the combined therapy of acupuncture and rehabilitation training, The control group was only treated with rehabilitation training. A contrastive analysis of the therapeutic effect of acupuncture combined with rehabilitation training and pure rehabilitation training was made after a treatment course of 3 months. The Gross Motor Function Measure (GMFM) and Beijing Gesell Developmental Scale were adopted to assess the neural development and rehabilitation outcomes of the two groups. In addition, skull MRI was adopted to evaluate the plerosis of injured cerebral nerve after treatment. Results: The total effective rate in treatment group was 87%, significantly higher than the 55% in the control group. The children’s development quotient (DQ) tested by Gesell Developmental Scale and scores tested by GMFM in the treatment group was obviously higher than the control group (P < 0.01). The improving and curing rates presented by skull MRI in the treatment group were higher than the control group (P < 0.01). Conclusions: Clearing the Governor Vessel and refreshing the mind Needling could accelerate the recovery of injured brain nerve and the reconstruction of brain function. The acupuncture therapy could ameliorate both the motor development and cognitive development. On the other hand, the forward curative effect of acupuncture combined with rehabilitation training was significantly better than the pure rehabilitation training.

Zhen-huan LIU

Nanhai Hospital for Women and Children, P.R.China

Title: A randomized controlled study and Evaluation of Children with Cerebral Palsy by Mind Acupuncture

Biography:

Abstract:

Day 2 : 2017-07-25

Session Introduction

Bin Zhang

2Icahn Institute of Genomics and Multi-scale Biology, USA

Title: Molecular Networks Shared by Parkinsonâ€™s Disease and Alzheimerâ€™s Disease

Biography:

Dr. Bin Zhang is a professor (pending) of the Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. His expertise lies in systems biology, machine learning and pattern recognition. He has developed a series of influential gene network inference algorithms which have been extensively used for identification of novel pathways and gene targets, as well as development of drugs for several major human diseases. As a prolific researcher, he has published a number of high profile papers in Nature, Science, Cell, Nature Genetics and PNAS. As of January of 2017, his publications have been cited 11,386 times.

Abstract:

Parkinson's diseases (PD) and Alzheimer's (AD) have been shown to share extensive clinical and pathological features. For example, most PD patients with dementia have neurofibrillary tangles and senile plaques. At the molecular level, dysregulation of pathways such as immune response and autophagy have been observed in both PD and AD. The latest genetics studies of PD and AD further reveal that polymorphisms in HLA, MAPT and PICALM are associated with both PD and AD. To systematically investigate the commonality in molecular interactions between PD and AD, we performed multiscale embedded gene co-expression network analysis (MEGENA) on a large cohort of gene expression data from over 150 PD brain samples and two large cohorts of RNA-sequencing data from over 800 AD brain samples. Microglia/immune enriched modules in AD and PD are most conserved (P=1.26e-209, 15 fold enrichment). The other conserved gene modules, which are involved in synaptic transmission, transmission of nerve impulse, monovalent inorganic cation transport and cholesterol metabolism, are significantly enriched for the respective differentially expressed gene signatures between disease and control, indicating common molecular mechanisms underlying the two neurodegenerative diseases. We further evaluated the network rewiring of these conserved modules between PD and AD. The converged, disease-associated molecular networks identified here not only reinforce the findings from PD and AD specific studies, but also provide a general framework to study the two diseases simultaneously.

Aisling Carr

National Hospital for Neurology and Neurosurgery, UK

Title: Thromboembolic risk in inflammatory neuromuscular disease patients on long-term intravenous immunoglobulin

Biography:

Aisling Carr works is a consultant neurologist on the Peripheral Nerve team in the National Hospital for Neurology and Neurosurgery where she leads the intravenous immunoglobulin service. Her areas of interest include diagnosis, treatment and patient-centered management of inflammatory neuromuscular diseases. She trained in Trinity College Dublin, Belfast Health and Social Care Trust Neurosciences Department, l’hopital Pitie de la Salpetriere Paris and the National Hospital of Neurology and Neurosurgery, Queen Square London.

Abstract:

Background Case reports and observational studies suggest that IVIg may be associated with an increased risk of thromboembolic events (TEEs), including myocardial infarction (MI), stroke, and venous thromboembolism.^1,2

The presence of traditional cardiovascular risk factors, the underlying condition or characteristics of IVIg administration have been proposed as contributory.^3,4

There is no guidance on risk management in patients who are potentially high risk but require ongoing IVIg treatment.

Aims: To ascertain (a) frequency of and (b) risk factors for thromboembolic events in a cohort of patients undergoing regular IVIg for neuromuscular disease.

Methods: Retrospective case note review of patients treated with regular IVIg for neuromuscular disease in our institution between Jan 2015-July 2016.

Diagnosis, dose, frequency, vascular risk factors, pre and post IVIg plasma IgG levels and viscosity were recorded..

Results: 112 patients were treated with IVIg during the study period.

Indications for IVIg were CIDP (61), Multifocal motor neuropathy with conduction block, (MMNCB) (41), other inflammatory neuropathies including CANOMAD and CISP (6) and other diagnoses including small sensory neuronopathy and inflammatory myositis (4).

Patients received a mean (S.D.) dose of IVIG of 1.6 (1.2) g/kg/month at a mean interval of 4.4 (3.0) weeks; range 1-18 weeks.

Twelve TEEs were documented during the study period including 6 MIs, 2 strokes and individual occurrences of DVT, TIA, PE and SVC obstruction secondary to line thrombosis.

	Population based rates* **	IVIg cohort*
TEE	7.6 (7.6,7.7)	53.6 (30.9,91.3)
ATE	6.5 (4.4,6.5)	35.7 (18.2,68.9)
VTE	1.2 (1.2,1.2)	22.3 (9.6, 51.2)
* per 1000 person years (95% CI) **Based on hospital admissions data 2014-16 NHS digital

· TEE risk did correlate with QRISK2 score (CVRF). However, one third of patients who had a TEE had a QRISK2 score of <20.

· IVIg dose g/kg/month and IVIg dose/day were not associated with an increased risk of TEE

· Lower âˆ† plasma IgG and lower post IgG plasma viscosity did not reduce the risk of TEE.

Conclusion

TEE rate is higher in inflammatory neuromuscular disease patients on longterm IVIg than that of the general population. Reduction of IVIg dose or infusion rate did not reduce this risk. Large scale, age, sex and CVRF-matched studies in IVIg treated(case) and IVIg naïve patients(control) are required to determine the quantify risk of TEE in attributable to this treatment and appreciate its thrombophilic mechanism.

Bruno Constantin

STIM Laboratory, CNRS, France

Title: Abnormal calcium entries and Calcium Channels in DMD : New therapeutic targets.

Biography:

Bruno Constantin is Research Director at CNRS and has his expertise in electrophysiology, cell biology and calcium channels and signaling. He worked on calcium signaling during skeletal muscle development during its phD thesis. He was recruited by CNRS in 1998 and has long studied the function of dystrophin in skeletal muscle and the mechanisms of calcium mishandling in Duchenne Muscular Dystrophy. His research was supported by AFM-Telethon in France, and this work highlighted the crucial role of TRP channels in the calcium alterations observed in DMD. He is nowadays the deputy director of STIM laboratory in Poitiers University and founded a new team working on calcium channels and signaling in stem cells.

Abstract:

Duchenne Muscular Dystrophy (DMD) is cause by the absence of dystrophin a cytoskeleton protein. The absence of dystrophin results in a loss of dystrophin-associated proteins at the sarcolemma such as syntrophin, and in calcium transfer deregulation through ion channels. This alteration in cell signalling may contribute to the death of muscle cells. The abnormalities in resting calcium permeability of DMD muscles have supported the idea of a small and persistent inward calcium leak leading to deleterious calcium mishandling. Studies on mouse muscle fibres also demonstrated that store-dependent calcium currents are more important in fibres from mdx dystrophic mice and we have shown that these Cation entries are restored by forced expression of a minidystrophin. Our group provided new insights by demonstrating the existence of a macromolecular complex including TRPC1 and TRPC4 channels associated with dystrophin and the adaptator Alpha1-syntrophin, which regulates through its PDZ domain the cation influx through TRPC. Consequently, the loss of dystrophin and Alpha1-syntrophin at the sarcolemma in DMD skeletal muscle leads to the loss of the repressing effect exerted on cation entries through TRPC channels. These disorders may be relevant for DMD physiopathological processes since overexpression of TRPC channels and increased calcium influx are sufficient for promoting the development of muscular dystrophy in mice. Elevation of calcium entry via TRPV2 cationic channels also promotes muscular dystrophy in animal models. Our studies on human muscle from DMD patients confirmed the alterations of Store-operated calcium entries and their regulation by syntrophin, as well as the implication of TRPV2 in additional abnormal entries. Moreover we also demonstrated that TRPV2 is also involved in abnormal constitutive calcium entries observed in ventricular cardiomyocytes from mdx dystrophic mice, and also in axial stretch-dependent influx. This cation channels could offer new therapeutic pharmacological targets, for counteracting calcium-induced muscle degeneration and cardiomyopathy in DMD.

Josef Finsterer

KAR, Vienna, Austria

Title: Central nervous system involvement in 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:

Statement of the problem: Central nervous system (CNS) disease is increasingly recognized as a manifestation of mitochondrial disorders (MIDs). However, the broad range of clinical CNS manifestation is still underestimated. This review aims at summarising and discussing previous and recent findings concerning the cerebral manifestations of MIDs.

Methodology & Theoretical Orientation: MIDs Literature review.

Findings: MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) either already at onset or later in the course. After the muscle, the brain is the organ second most frequently affected in MIMODS. Cerebral manifestations of MIDs are variable and may present with or without a lesion on imaging or functional studies but there can be imaging/functional lesions without clinical manifestations. The most well-known cerebral manifestations of MIDs include stroke-like episodes, epilepsy, headache, ataxia, movement disorders, hypopituitarism, muscle weakness, psychiatric abnormalities, nystagmus, white and grey matter lesions, atrophy, basal ganglia calcification, and hypometabolism on FDG-PET. For most of the MIDs only symptomatic therapy is currently available. Symptomatic treatment should be supplemented by vitamins, co-factors, and antioxidants.

Conclusion & Significance: cerebral manifestations of MIDs need to be recognised and appropriately managed since they strongly determine the outcome of MID patients.

LIU ZHEN-HUAN

Nanhai Maternity Children'sHospital of Guangzhou University of Chinese Medicine, China

Title: Effects of Quality of Life of Autistic Disorder Children

Biography:

Abstract:

Abstract:ã€Objectiveã€‘ To investigate quality of life in Autistic Disorder children. ã€Methodã€‘ PedsQL4.0 was used to measure quality of life of 200 children with Autistic Disorder and 120 normal children. ã€Resultsã€‘The quality of life of Autistic Disorder group was lower than normal group in the scores of physical functioning were(62.30±25.05),emotional functioning were(53.57±26.69),social functioning were(44.63±27.91)ï¼Œand school functioning(38.69±30.60).The totals cores of PedsQL were(49.86±23.32),with the difference being significant(90.16±13.32ã€79.09±19.56ã€86.39±15.45ã€82.75±16.03ã€85.23±14.2ï¼ŒP<0.01). ã€Conclusionã€‘ Children with Autistic Disorder took grievous influence on quality of life.

Scientific Program

Day 1 : 2017-07-24

Keynote Forum

Keynote: will update soon

Biography:

Abstract:

Session Introduction

Title: Elucidation of the molecular mechanisms associated with early onset primary dystonia (DYT16) caused by mutations in PACT

Biography:

Abstract:

Title: Reduction of crosstalk in surface electromyogram by optimal spatio-temporal filtering

Biography:

Abstract:

Title: Arbovirus infections of nervous system â€“ trends and threats

Biography:

Abstract:

Title: A randomized controlled study and Evaluation of Children with Cerebral Palsy by Mind Acupuncture

Biography:

Abstract:

Title: A randomized controlled study and Evaluation of Children with Cerebral Palsy by Mind Acupuncture

Biography:

Abstract:

Day 2 : 2017-07-25

Session Introduction

Title: Molecular Networks Shared by Parkinsonâ€™s Disease and Alzheimerâ€™s Disease

Biography:

Abstract:

Title: Thromboembolic risk in inflammatory neuromuscular disease patients on long-term intravenous immunoglobulin

Biography:

Abstract:

Population based rates* **

IVIg cohort*

TEE

7.6 (7.6,7.7)

53.6 (30.9,91.3)

ATE

6.5 (4.4,6.5)

35.7 (18.2,68.9)

VTE

1.2 (1.2,1.2)

22.3 (9.6, 51.2)

* per 1000 person years (95% CI)

**Based on hospital admissions data 2014-16 NHS digital

Conclusion

Title: Abnormal calcium entries and Calcium Channels in DMD : New therapeutic targets.

Biography:

Abstract:

Title: Central nervous system involvement in mitochondrial disorders

Biography:

Abstract:

Title: Effects of Quality of Life of Autistic Disorder Children

Biography:

Abstract:

Day 3 : 2017-07-26