Dr. Yusei Miyazaki is the chief neurologist and director of the multiple sclerosis/neuromyelitis optica spectrum disorder (MS/NMOSD) clinic at Hokkaido Medical Center (Sapporo, Japan). He graduated with an M.D. from Hokkaido University (Sapporo, Japan) in 1998. Following residency in internal medicine and neurology, he earned a Ph.D. in neuroimmunology in 2007 from Hokkaido University. Thereafter, he continued his post-doctoral research training at the National Center for Neurology and Psychiatry (Tokyo, Japan) and at McGill University (Montreal, Canada) as part of a Government of Canada Post-Doctoral Research Fellowship. As a physician-scientist, Dr. Miyazaki conducts basic and clinical research on MS/NMOSD and has more than 70 research publications in this field.

Abstract of Talk:

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) clinically characterized by recurrent attacks of neurological symptoms. Most patients have anti-aquaporin 4 autoantibodies in the circulation. Upon breakdown of the blood-brain barrier, these autoantibodies penetrate the CNS and trigger destructive inflammation. Progression of disability in NMOSD is dependent exclusively on the occurrence of attacks. With the exception of rituximab, treatments for preventing NMOSD relapse basically worked through nonspecific immunosuppression and had incomplete effectiveness as well as a broad spectrum of side effects. In 2019 and 2020, the effectiveness of four monoclonal antibodies—eculizumab, satralizumab, inebilizumab, and rituximab—was demonstrated one after the other in randomized controlled trials, and the results have led to the approval of these drugs in many countries. All these monoclonal antibodies have definite effectiveness in preventing NMOSD relapses with acceptable safety profiles. With the advent of these monoclonal antibody therapies, the treatment of NMOSD has entered a new era. In this lecture, I will share our experience treating NMOSD using these new monoclonal antibodies and discuss the best treatment strategy for NMOSD at present.

Dr Sudarshini Ramanathan is a neurologist and clinician-scientist, with subspecialty expertise in neuroimmunology. Dr Ramanathan is a staff specialist neurologist at Concord Hospital in Sydney. She completed her PhD and postdoctoral fellowship in neuroimmunology at the University of Sydney, and was a senior postdoctoral fellow at the University of Oxford working with the Oxford Autoimmune Neurology Group. She now leads a fundamental science and clinical research program and heads the Translational Neuroimmunology Group at the University of Sydney. Dr Ramanathan has received 14 continuous years of NHMRC fellowship funding, and is currently an NHMRC Investigator Fellow. She has authored over 60 publications in the field of autoimmune neurology. In 2013, Dr Ramanathan established and has since been the lead investigator of the Australasian MOGAD Study Group, which encompasses over 150 clinicians from 45 centres in Australia, New Zealand, and South East Asia. She leads the evaluation of a cohort of over 700 children and adults with myelin oligodendrocyte glycoprotein antibody-associated disease. Dr Ramanathan’s research program is focused on understanding the underlying immunobiology of autoimmune neurological disorders, in order to improve the diagnosis and treatment of patients who otherwise risk significant disability.

Abstract of Talk:

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is now recognised as a disease entity distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. This presentation will highlight the scientific and clinical evolution of our understanding of this condition, and the role of laboratory biomarkers and their strength and limitations in characterising this disorder. We will review the expanding clinical spectrum of MOGAD, and the clinical and radiological profiles which can distinguish this condition from other demyelinating syndromes and facilitate expedited diagnosis. This presentation will outline the development of the 2022 International MOGAD Diagnostic Criteria, and discuss therapeutic decision making both at disease onset and in the case of relapsing disease.

Dr. Wee Yong is a Professor at the University of Calgary. He leads the Multiple Sclerosis (MS) research program at the university and he directs the provincial Alberta MS Network. Dr. Yong has been the President of the International Society of Neuroimmunology, and he continues to co-direct its Americas and Global Schools of Neuroimmunology. Dr. Yong’s research interests lie in the area of neuroimmunology, neuroprotection and CNS regeneration, and his projects are guided by MS, glioblastoma and intracerebral hemorrhage. He has published 370 peer-reviewed manuscripts and his research has been translated into Phase 2 and 3 clinical trials in MS; his team has an ongoing Phase 1/2a trial in glioblastoma. His work has been cited over 36,000 times (h-index of 107) according to Google Scholar. Dr. Yong is an elected fellow of both the Canadian Academy of Health Sciences and the Royal Society of Canada. He received the 2017 Allyn Taylor International Prize in Medicine for ‘transformational discoveries in MS’. Dr. Yong was profiled in the August 2021 issue of the world’s #1 clinical neurology journal, Lancet Neurology.

Abstract

The slowly expanding lesion (SEL) detected by brain imaging grows gradually over years in the brain of people living with MS, particularly those with progressive MS. The number of SELs has been correlated with progression of disability. Analysis of postmortem MS samples highlights pro-inflammatory microglia at the rim of SELs, and several of these have iron deposition in their midst. Correspondent with these features are accumulation of oxidized phosphatidylcholines and signs of axonal pathology. In tissue culture, our studies show that ferrous iron, oxidized phosphatidylcholines and pro-inflammatory microglia are toxic to neurons (e.g. Dong et al., Nature Neurosci 2021). While we lack medications to antagonize iron or oxidized phosphatidylcholines in SELs, the toxicity of microglia may be ameliorated by repurposed hydroxychloroquine and the family of Bruton’s tyrosine kinase inhibitors (e.g. Yong, Neuron, Epub ahead of print).

Professor Taylor has been undertaking research into the genetic and environmental factors that are associated with the onset and progression of multiple sclerosis for more than 25 years. His work has focused on vitamin D and sunlight exposure as well as the role of infection with the Epstein Barr virus and other herpes viruses. He is a professorial research fellow at the Menzies Institute for Medical research University of Tasmania and currently holds an Australian National Health & Medical Research Council Leaders Fellowship. He has published over 380 papers and has an H Index of 70, his work has been cited more than 25000 times. He is currently an associate editor for the Journal of Neurology Neurosurgery and Psychiatry.

Abstract of Talk:

Epstein Barr Virus EBV is a ubiquitous human herpes virus that is known to be associated with several human illnesses including MS. Recent work has indicated that infection with EBV is an obligate risk factor for developing MS and that there may be molecular mimicry between EBV epitopes and CNS proteins. These important recent discoveries have raised the possibility of targeted therapies against EBV, or even vaccination against EBV as potential therapeutic options in the prevention or treatment of MS. This lecture will examine the current understanding of the role of EBV in MS causation and progression, the role of immunotherapy including T Cell therapies, and antivirals in the treatment of MS the potential role of anti-retroviral therapies in EBV control and the controversies surrounding the potential benefits and harm from an EBV Ivaccine

Dr Pin Fee Chong is currently with the department of Pediatrics, Graduate School of Medical Science, Kyushu University, Japan. His educational and academic appointments are as follows: 2006 M.D. Kyushu University, School of Medicine, Fukuoka, Japan 2006-2008 Internship in Medicine, Fukuoka Tokushukai Hospital 2008-2011 Residency in Pediatrics, Fukuoka Tokushukai Hospital 2011-2014 Residency in Child Neurology, Fukuoka Children’s Hospital 2014 -2021 Fukuoka Children’s Hospital (Dept of Child Neurology, Dept of General Pediatrics & Interdisciplinary Medicine) 2021- Current Position He is a certified board member of Japan Pediatric Society, Japanese Society of Child Neurology and Japan Epilepsy Society. His area of interest is in Pediatric neurological disorders, especially in inflammatory and infectious disease of the central nervous system. He has more than 30 publications in the area of pediatric neurological disorders including demyelinating disorders, encephalitis, acute flaccid myelitis, epilepsy, genetics, and others.

Abstract of Talk:

Over the past few years, autoantibodies against myelin oligodendrocyte glycoprotein (MOG-Abs) have been consistently identified in a variety of demyelinating syndromes. Although MOG-Abs were initially reported in children with acute disseminated encephalomyelitis (ADEM), the clinical spectrum of these MOG-Ab-associated disorder (MOGAD) is expanding and somehow differs between pediatric and adult patients. Recent studies using cell-based assays have demonstrated a higher frequency of MOG-Abs detection in pediatric than adult patients with acquired CNS demyelinating diseases. Typical pediatric MOGAD presentations usually show ADEM in younger, and optic neuritis and transverse myelitis in older children (age >9 years). A proportion of these children experience a relapsing disease course. Until recently, clinical and radiological evaluation has expanded the spectrum of MOGAD including those showing atypical features such as encephalitis- or leukodystrophy-like appearance and other unclassifiable phenotypes. While there is a lack of knowledge about the pathogenic roles of MOG, an increasing number of studies have shown that MOG is a protein that can elicit demyelinating immune response in animals. This review discusses the diversity in clinical phenotypes in pediatric MOGAD and present our recent data from both clinical and experimental perspectives.

Professor Russell Dale is a Paediatric Neurologist and clinical academic at the Children’s hospital at Westmead and University of Sydney. He is Head of Clinical School and Head of Speciality of Child and Adolescent Health of University of Sydney, and Clinical Director of the Kids Neuroscience Centre, a research group of 110 clinicians and scientists. He is an internationally recognised researcher in immune and autoimmune disorders of the brain, and neurodevelopmental and movement disorders of childhood. He has published 315 peer reviewed publications; his work has been cited 22,200 times and his H index is 76 (Google Scholar). His work has resulted in therapies for immune mediated brain disease being approved by government agencies and academic societies around the world, such as National institute for Clinical Excellence, American Academy of Neurology, and European League of Rheumatology. He has led international consensus guidelines for the treatment of autoimmune brain disease in children and been senior author on discovery papers of essential diagnostic biomarkers which are now part of routine clinical care around the world. He has been awarded over $18M in research funding and is a current NHMRC Leadership fellow (2021-5).

Abstract of talk:

A considered approach is required to the child or adolescent with acute or relapsing demyelination of the CNS. Firstly, the underlying clinical and syndrome and underlying pathophysiology differs in the very young child: The young child is more likely to present with acute disseminated encephalomyelitis (ADEM) or bilateral optic neuritis than an adult. In a young child with new onset CNS demyelination, it is more likely they have MOG antibody associated disease than multiple sclerosis. In the adolescent, multiple sclerosis becomes the more likely diagnosis in the child presenting with CNS demyelination. This distinction is essential, because the therapeutic approach is different between the autoantibody associated syndromes (MOGAD or AQP4 ab disease) and multiple sclerosis. Secondly, neuroinflammation is inherently problematic to the developing brain, and can result in disruption of synaptic connectivity, and consequently neurodevelopment. Hence, treating neuroinflammation speedily and adequately, is an important consideration. The cognitive sequelae of multiple sclerosis in adolescents, and neurodevelopmental problems such as ADHD after ADEM, are increasingly recognised. Thirdly, balancing the need for adequate immune modulation with side effects of treatment is important, to avoid harmful side effects to the young. Thankfully there is now good safety data regarding the use of immune therapies in children and adolescents with CNS demyelination, to aid the clinician in decision making. Fourthly, therapeutic compliance is a major consideration in the adolescent, and combination of respectful education plus empowerment is important.

Professor Ju-Hong Min is currently with the Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University Her areas of interest are in Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein-Associated Disorder, Demyelination, and Remyelination
Licenses and Certifications:
• 2000, License, Korean Medical Board (69696) • 2005, License, Korean Neurology Board • 2009, Certificate, Clinical Neurophysiology EMG & EP, The Korean Society for Clinical Neurophysiology
Membership: • Member, Korean Neurological Association • Member, American Academy Neurology • Member, Korean Society of Clinical Neurophysiology • Editorial Board Member, Korean Society of Neuromuscular disorder • Chair of Academics Committee, Korean Society of Pain & Autonomic Disorders (2020. 3~) • Editorial Board Member and Assistant administrator, Korean Society for Multiple Sclerosis • Chair of Academics Committee, Korean Society for Neuroimmunology (2020. 3~) • Advisory Board Member, Health Insurance Dispute Mediation Committee (2021. 1~)

Abstract of talk:

Immunosenescence is a process of immune dysfunction with aging and includes changes in the composition and function of lymphoid organs in the elderly. This is closely related to the development of autoimmunity and neurodegeneration and can contribute to co-morbidities in aging population. With increased life span and effective disease modifying therapies (DMTs), the number of elderly patients with CNS demyelinating diseases is growing. In addition, late-onset patients with such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody associated disorder (MOGAD) show different clinical characteristics, compared to early-onset patients, although the interactions of immunosenescence with pathomechanisms remain unclear. Particularly in MS, current DMTs reduce relapse activity and slow disease progression, but cannot prevent the accumulation of disability, which may be explained by the impact of immunosenescence on the immune system and disease progression. Moreover, most clinical trials for DMT were not designed focusing on aging patients and the risk of their comorbidities can negatively affect the disease course, which can make the therapeutic strategies more challenging in elderly patients with CNS demyelination.

Dr Ho Jin Kim is a consultant neurologist and principal scientist at the Research Institute and Hospital of National Cancer Center, Goyang Korea. He is also professor of Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science & Policy. Dr. Kim received his medical degree from Seoul National University where he also completed his residency training in neurology and clinical fellowship in multiple sclerosis (MS) and neuromuscular disease. Dr. Kim went on to pursue his academic research interest as a research fellow in neuroimmunology at the University of Southern California, Keck School of Medicine, Los Angeles, California, USA for a year. Then he spent four years as a senior fellow and staff researcher in MS and neuroimmunology at the Montreal Neurological Institute of McGill University, Montreal, Quebec, Canada. His major research interests lie in studying the development and application of biological assays to monitor the disease process and evaluate the response to novel therapeutics. His other research interests are in studying differences among various autoimmune inflammatory diseases of CNS including MS, neuromyelitis optica spectrum disorder and MOG-IgG associated disease in both clinical and radiological features as well as underlying pathogenesis. He is currently the Vice-President of PACTRIMS.

Abstract of talk:

Multiple sclerosis (MS), aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) are three main relapsing form of autoimmune CNS diseases. In MS, the major burden of disability is thought to be a consequence of progressive disease independent of clinical attacks and new MRI activity. By contrast, attack-independent progression appears extremely rare in AQP4-IgG+ NMOSD and MOGAD, where disability is thought to derive almost exclusively from severe attacks, resulting in permanent tissue damage and poor recovery.

In the same vein, subclinical neuroaxonal damage in the absence of overt clinical attacks occurs in all stages of MS, while it is yet a matter of controversy in AQP4-IgG+ NMOSD and MOGAD. Identifying such an attack-independent tissue damage is essential, as it should be accounted for when evaluating treatment response, in order to achieve best clinical outcome. In this talk, I will review and discuss the current evidence on the occurrence of subclinical attack-independent tissue damage in patients with AQP4-IgG+ NMOSD and MOGAD.

Dr Jin Nakahara is based in Tokyo, Japan as a Professor and Chair of the Department of Neurology at Keio University School of Medicine. He is also a Deputy-Director of the Keio University Global Research Institute and a Visiting Professor of Kanazawa University. Professor Nakahara received his M.D. from the Keio University School of Medicine in 2003 and his Ph.D. from the Keio University Graduate School of Medicine in 2007. More than 70 articles in the field of neurology has been published in leading international journals, such as Developmental Cell, The Journal of Clinical Investigation, and Nature Neuroscience. He holds active memberships with many professional societies in Japan and abroad, and he is the current Director of the Japanese Society of Neuroimmunology. He also serves as a committee member of the Central Organizing Committee of Pan- Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS), a Delegate of the Japanese Society of Neurology, and a Councillor of the Japanese Society of Internal Medicine.

Abstract of talk:

The T2 lesion on magnetic resonance imaging (MRI) remains the most important paraclinical tool to identify demyelination and to diagnose multiple sclerosis (MS). However, the clinico-radiological paradox has been well recognized: There are only modest correlations between irreversible neurological disability and T2 lesion load in MS. Given the increasing number of available disease-modifying drugs (DMDs) with varying mechanisms of action, precise evaluation of individual MS immuno-pathology and neurodegeneration with advanced imaging may identify those who are at a risk of progressive disease course and ultimately lead to better choice of DMD to improve his/her prognosis. In the current lecture, current imaging modalities and their potential utility in MS will be reviewed and summarised.

Dr Lekha Pandit is the Professor of Neurology and Director of Centre for Advanced Neurological Research at Nitte University, Karnataka, India.
Honours:
• Fulbright Nehru scholar- Academic & Professional excellence- 2018
• Visiting Professor of Neurology, Harvard Medical School –2018 Sept-2019 Mar.
• Nominated member Central organizing committee of PACTRIMS (2015- present)
• Nominated member of International Medical Consortium of Guthy Jackson NMO Foundation, USA (2014- present)
• India representative of Multiple sclerosis International Federation Medical board (2014- 2018)
• Visiting Scholar, Addenbrookes hospital (MS genetic group), Cambridge, UK (2011-2012)
• Jacqueline Du Pre awardee (MSIF,UK)- 2012
• Research fellow- Demyelinating disorders- University of Newcastle upon Tyne (1995-1997)
Her area of Interest is in research and clinical management of CNS Autoimmune disorders and she has published over 150 peer reviewed papers and 16 chapters

Abstract of talk:

Vaccinations are integral to preparing patients for long term immunotherapy in autoimmune disorders such as multiple sclerosis. Vaccinations on one hand protect patients on disease modifying therapy against specific infections, but on the other, may have varied efficacy on these very patients by virtue of their underlying disease and concurrent medications. In addition, vaccination may trigger new / first attack of a demyelinating disorder. Geographically, susceptibility for specific infections vary and patients with multiple sclerosis may be on disease specific or “off label” therapies. These in turn increase the challenges in advocating vaccinations and especially timing of the latter in relation to ongoing therapy. The COVID-19 pandemic and COVID-19 vaccinations offer a good example for analysing the relationship between vaccinations, MS and immunotherapy. A review of real-life based evidence on vaccinations in MS patients on immunotherapy, including in a low- middle income set up will be presented.

Stephen Reddel is a staff specialist neurologist at Concord Repatriation & General Hospital Sydney, and consultant neurologist at the Brain & Mind Research Institute, University of Sydney. He trained in neurology at Royal Prince Alfred Hospital, Sydney, and at the Radcliffe Infirmary, Oxford, and has a PhD in the immunology of the Anti-Phospholipid Syndrome.
Stephen Reddel and Sean Riminton founded the first Australian neuroimmunology clinic at Concord Hospital, which specialises in the safe treatment of neurological conditions requiring immunotherapy, including multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and a host of rarer diseases.
He has a longstanding interest in clinical safety. This focus on safety has also included www.immunosuppressionscreen.net, and in 2014 the Alemtuzumab in MS Safety Study (AMS3), and multiple invited international presentations.
Dr Reddel’s academic appointment is Associate Professor, Sydney University where he has been involved in the neurology course development, ensuring standards of institutional sartorial elegance, online lectures and teaching of medical students, post graduate clinical training and post graduate research student supervision. He serves as the chair of the neurology working group for immunoglobulins and as the representative on the National Immunoglobulin Government Advisory Committee (NIGAC).
He has research interests in myasthenia gravis, examining the function of anti-MuSK antibodies and the homeostasis of the neuromuscular junction; in neuroimmunology and MS, and in neurogenetics including the muscular dystrophies and inherited neuropathies. Funding support in the last 5 years has included NH&MRC and the muscular dystrophy associations of the USA and NSW. He has published in journals including Brain, Annals of Neurology and Current Opinion in Neurology in this period.

Abstract of talk:

Autoimmunity in increasingly recognised as a cause of human and neurological disease, and unlike many diseases is treatable. The alloimmune response is not necessarily the same as the autoimmune response. The alloimmune response has prominent pattern recognition pathways (danger signals), innate immune system responses, and redundancy of pathways for defending against the pathogen.
Nevertheless as a general principle it is safer to assume that immunosuppressive drugs are likely to affect an alloimmune pathway that exists to fight an infection, at some time, somehow, somewhere. The absence of a signal in a selective population controlled randomised trial does not prove that such a drug is without risk in the real world application.
The recent global pandemic has illustrated how mechanisms of alloimmunity in the context of particular immunosuppression can anticipate what happens in a real test not seen in trials, for instance with pulsed anti-CD20 monoclonals in COVID-19 severity and vaccination responses. There are many other anticipatable risks for infection with our therapies that will be discussed.
The discussion of the infectious consequences of immunosuppression is not to undermine the excellent benefits of therapy, but it may influence choice, assist in screening and to diagnose events when they occur.

Professor Hartung is Professor of Neurology at Heinrich-Heine-University Düsseldorf, Honorary Professor, Brain and Mind Center, University of Sydney, Visiting Professor at Medical University Vienna and Palacky University Olomouc. Professor Hartung’s clinical and translational research interests are in the field of basic and clinical neuroimmunology, particularly exploring new treatments. He was President of ECTRIMS and is executive board member of the European Charcot Foundation. He has served on the SC and DMC of many phase 2 and 3 trials in MS, NMOSD, CIDP and GBS. He has authored more than 1060 articles in peer-reviewed journals and is a Highly Cited Researcher 2017, 2018, 2020. He is / has been on the editorial board of several journals.
Professor Hartung is a Fellow of the American Academy of Neurology, Corresponding Fellow of the American Neurological Association, Fellow and General Assembly member of the European Academy of Neurology, Honorary Member of the All Russian Neurological Society, Honorary Member of ECTRIMS, Honorary Member of the French Neurological Society, Honorary Member of the Polish Neurological Society, Member of the Association of British Neurologists and a Fellow of the Royal College of Physicians (London).

Abstract of talk:

Biomarkers encompass imaging and molecular biomarkers reflecting pathobiology, disease state and activity. Molecular biomarkers in MS can be determined in blood, CSF and saliva.
Fluid phase biomarkers serve different functions. They can be diagnostic, prognostic, indicate disease activity, and represent therapeutic response markers. Extensive research has been carried out using hypothesis and non-hypothesis driven approaches. I will review CSF and blood markers emphasizing the role of IgG and IgM oligoclonal bands, cytokines, chemokines, microRNAs and neurofilament light chains. The latter has emerged as the most robust fluid phase biomarkers in MS examined to date.

Heinz Wiendl studied medicine in Germany, Switzerland, and the USA, graduating in 1996. After working as a research fellow at the Institute of Neuroanatomy, Nuremberg, and the Max Planck Institute for Neurobiology and the Department of Neurology, Tuebingen, he became head of the clinical research group for multiple sclerosis (MS) in Wuerzburg in 2005 and acted as a vice-chair of the Department of Neurology. In 2010, he was recruited to the University Hospital Muenster as director of the Department of Neurology – Inflammatory Disorders of the Nervous System and Neurooncology. Since 2013, Prof. Wiendl serves as head of the Department of Neurology, Muenster – to which the Institute of Translational Neurology has been associated since 2018. His research focuses on inflammatory neurodegeneration and immune regulation and protection as well as monitoring MS and its therapy. His achievements have been recognized by both Sobek awards of the German Society for MS (DMSG) (2004; 2015). In 2017, he was appointed Honorary Professor at Sydney Medical School and in 2020 he received an honorary doctorate from the Medical Faculty of Masshad/Iran. Heinz Wiendl is a member of numerous scientific and academic advisory boards and expert panels, including editorial boards of international scientific journals in the fields of neurology, neurosciences, and immunology, as well as for societies, foundations, and project promoters. Currently, he is the speaker of the Collaborative Research Center 128 "Multiple Sclerosis", and speaker of the disease-related competence network
Multiple Sclerosis (KKNMS). He is the founder and principal investigator of the "Body and Brain Institute" Muenster, a prestigious research building funded by the German Federal Ministry.

Abstract of talk:

Current therapies for multiple sclerosis (MS) effectively reduce relapses and relapse-associated worsening caused by transient infiltration of peripheral immune cells into the CNS. However, they are less effective at slowing disability accumulation in both relapsing and progressive MS, possibly because they do not penetrate the blood-brain barrier (BBB) to act on CNS-resident innate immune cells that have been proposed to drive disability.
Bruton’s tyrosine kinase (BTK) is an intracellular signaling molecule regulating maturation, migration, survival, and activation of B cells and myeloid cells, particularly microglia. B cells and microglia are central players in MS immunopathogenesis and contribute to disease progression. As such, CNS-penetrant inhibitors of BTK (BTKis) hold promise to target adaptive and innate immunity concurrently on both sides of the BBB. Originally developed as a B-cell malignancy treatment, BTKis emerge as a promising therapeutic approach on the horizon of MS treatments. Currently, five BTKis are undergoing clinical trials in MS. These BTKis differ in selectivity, strength of BTK inhibition, binding mechanisms, and ability to modulate immune cells within the CNS. Here, BTK function in signaling pathways of different immune cells relevant to MS will be reviewed, and overview of preclinical data and clinical trial results will be provided.

Riwanti Estiasari is an Associate Professor in Neurology Department Faculty of Medicine Universitas Indonesia. She works as Neurologist in Cipto Mangunkusumo hospital Jakarta.

Her work is focused on Neuroimmunology especially Multiple Sclerosis, NMOSD and autoimmune encephalitis and Neuroinfection. Until now she already has around 70 publications.

Riwanti actively educate patients through Indonesia Multiple Sclerosis Foundation. She also has passion in medical education.

Abstract of Lecture:

Multiple sclerosis is a demyelinating disease that has the potential to cause disability and affects many young people. MS is mainly found in Western countries. Although the number is not as high as in Western countries, the prevalence continues to increase in Asia Pacific. In diagnosing MS, one thing that needs to be considered is to differentiate the clinical findings from infectious diseases, especially those endemic in Asian countries.

The clinical symptoms of central nervous system infection can resemble MS and the imaging features. Since the management will differ, distinguishing between the two is very important.

Screening before starting treatment is also essential to ensure no latent infection in the patient.

Some common infections, such as tuberculosis neurocysticercosis, can appear similar to MS. Other diseases that also need attention include hepatitis C, Progressive Multifocal Encephalopathy, syphilis, and HTLV-1.

It is essential to exclude the possibility of an infectious disease early in diagnosing MS. The findings of infectious diseases can affect the diagnosis that is made and the treatment that will be given.

Giancarlo Comi is honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, Milan, Italy. He is the President of the European Charcot Foundation (ECF), and since 2013 has served as vice chair of the Progressive Multiple Sclerosis Alliance and co-chair of the Industry Forum of the Alliance. He holds the office of president of the European Neurology Society, of the Italian Society of Neurology and of the Italian Society of Clinical Neurophysiology. He is fellow of the European Academy of Neurology (EAN).

In recent years, Professor Comi has received the ‘Gh. Marinescu’ honorary award from the Romanian Society of Neurology and has been awarded honorary memberships of the Russian Neurological Academic Society, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), the European Neurological Society (ENS), the Sociedad Espanola de Neurologia, the Société Francaise de Neurologie. He also received in 2015 the Charcot Award for MS Research from the MS International Federation (MSIF). In the past year Professor Comi was awarded the Gold Medal of ‘Benemeranza Civica’ from the City of Milan and has been recently conferred the honor of merit as Official of The Italian Republic by the President of Italy.

The main areas of scientific interest include clinical neurophysiology, neuroepidemiology and multiple sclerosis, with special interest treatment and monitoring on inflammatory diseases of the peripheral and central nervous system. He has been principal investigator of many phase II and III multiple sclerosis clinical trials.

Prof. Comi has authored and co-authored more than 1000 articles in peer-reviewed journals, and edited several books, with an h-index of 114. He has been organizer and/or invited speaker for more than 500 conferences, both nationally and internationally. He is co-editor of Neurological Sciences and member of the editorial boards of many international journals.

Abstract of Lecture:

The traditional classification of multiple sclerosis courses in relapsing-remitting, primary progressive and secondary progressive has been recently challenged by the evidence that a silent progression may occur quite early, perhaps already in the preclinical phase of the disease. Early detection of the progression is very important because the pathophysiological mechanisms underlying progression are different from those operating in the relapsing phase of the disease and require a different therapeutic approach. The values and limits of the different approaches for the ascertainment of silent progression will be discussed.

The recent availability of disease modifying treatments for primary and secondary progressive multiple sclerosis requires the availability of tools for assessment of treatment response. The expanded disability status scale (EDSS) is the gold standard in clinical trials and also in clinical practice, however in a recent study it was demonstrated that EDSS is more amenable to measurement error and less sensitive to changes than other outcome measures, such as T25FW and 9HPT. These alternative outcome measures are mostly used for research purposes, as a consequence the detection of a treatment failure in progressive MS patients can be late and incorrect. This is a relevant problem because patients with PMS are more exposed to risks of adverse effects of DMTs due to age, more frequent comorbidities and disability. The contribution of imaging, functional and body fluid biomarkers in progressive multiple sclerosis monitoring will be examined.

Todd Hardy is a Senior Staff Specialist Neurologist at Concord Hospital, Co-Director of the MS Clinic at the Brain and Mind Centre and a Clinical Associate Professor in Medicine at the University of Sydney. He is Co-Editor of Advances in Clinical Neuroscience and Rehabilitation and sits on the editorial board of the Journal of Neuroimmunology and Frontiers in Neurology. He trained in neurology at Concord and Royal Prince Alfred Hospitals in Sydney, and at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. His research interests are in the field of MS and its differential diagnosis including atypical forms of demyelination, and other central nervous system inflammatory diseases, especially Susac’s syndrome. He leads the Australian Susac’s Syndrome Database (SuSAD), one of the world’s largest repositories of information on Susac’s syndrome. He has published more than 90 articles including in The Lancet, Lancet Neurology, Nature Communications, Nature Genetics, JAMA Neurology, and JNNP.

Abstract of Lecture:

There are now substantial data from DMT clinical trials, extension studies, and real-world MS registries that early treatment, especially with high efficacy disease modifying therapies, improves outcomes in MS. This has been reflected in successive iterations of the McDonald criteria for the diagnosis of MS which have enabled earlier recognition facilitating earlier treatment.

Despite the high sensitivity of the McDonald criteria, specificity is low, and misdiagnosis of MS is common - mainly due to a failure to apply the criteria correctly. Numerous conditions have the potential to mimic MS and the McDonald criteria were not designed to distinguish MS from other conditions. A new revision of the McDonald criteria is currently underway and an important topic for consideration will be if an even earlier diagnosis is possible. The downside of trying to diagnose and treat MS earlier is a risk of overdiagnosis and misdiagnosis.

This talk will address the need for early MS diagnosis and the potential for MS misdiagnosis with examples of red flags that cast doubt upon the diagnosis of MS. It will also cover new advances with the potential to improve the specificity of MS diagnosis.

Professor Tomas Kalincik is Dame Kate Campbell Professorial Fellow, the head of the Clinical Outcomes Research (CORe) Unit at the University of Melbourne and of the Neuroimmunology Centre at the Royal Melbourne Hospital.

Together with his research group, CORe, Tomas specialises in analytics of observational data in neurology. He has led a number of international collaborative research initiatives - including studies of comparative effectiveness of MS therapies, management of treatment failure and individual treatment response. He has published more than 188 articles in peer-reviewed journals, including JAMA, Lancet Neurology and Brain. His main research interests span treatment outcomes in MS and other neuroimmunological diseases, individualised therapy, prognostics (including emerging biomarkers), causal inference, epidemiology and utility of volumetric MRI. He worked with the MS International Federation and WHO on scoping the first WHO Essential Medicines List for MS. He is the vice-chair of the Scientific Leadership Group of the global MSBase registry, and collaborates with multiple national MS registries. Tomas convenes the international CORe Advanced Statistics Course, endorsed by the European Committee for Treatment and Research in MS, co-chairs the scientific committee of the MS Australia Progress in MS Research conference, and convenes preceptorships for neurologists and nurses at the RMH Neuroimmunology Centre.

Abstract of Lecture:

Earlier this year the World Health Organisation has reached a landmark decision to include, for the first time, disease modifying therapies for multiple sclerosis on the Essential Medicines List. This is a culmination of a large effort led by the MS International Federation and the Cochrane MS and Rare Diseases of the CNS Review Group, with support form two expert and consumer panels over a the last two years. Tomas, who took part in this work, will talk about the synthesis of the evidence, the rationale for the proposal and the therapies that constitute the first entry for MS on the WHO Essential Medicines List.

Dr Kaskow completed her PhD in Genetics at the University of Western Australia and six years of postdoctoral research under world-renowned neurologists Dr Philip De Jager and Dr Howard Weiner and immunology researcher Dr Clare Baecher-Allan at the Ann Romney Centre for Neurologic Diseases at Brigham and Women’s Hospital, Harvard Medical School and the Broad Institute of Harvard and MIT. Her research focuses on effector and regulatory T and B cells in Multiple Sclerosis and other neurologic diseases as well as identifying the antigen(s) responsible for MS. In 2021, Dr Kaskow joined Professor Allan Kermode’s lab in the Demyelinating Diseases group at the Perron Institute as a post-doctoral scientist and received the inaugural Eyewall Foundation Post-Doctoral Award. Dr Kaskow has 12 publications with over 1400 citations and an average FWCI of 3.77.

Current position: Post-doctoral Scientist

Areas of Interest: Antigen Discovery, Regulatory T and B cells, Functional genetic variants

Number of publications: 12

Abstract of Lecture:

Single-cell techniques enable the detailed analysis of individual cells with high resolution across the epigenome, transcriptome, and/or proteome. Unlike multicellular studies, single-cell methodologies facilitate the recognition of matched alpha and beta chains of T cell receptors (TCRs) which can be harnessed to generate a functional TCR, allowing thorough exploration in assays to identify its cognate antigen. Recent advances in epitope discovery assays have revolutionized the unbiased screening of both the virome and human proteome providing powerful tools to uncover disease-related exogenous and endogenous antigens. Additionally, tissue-specific techniques including single-nucleus technologies provide new avenues for investigating CNS infiltrating immune cells behind the blood-brain barrier shedding light on the pathogenic mechanisms occurring within MS lesions.

Makoto Kinoshita, M.D., Ph.D. graduated from Osaka University Medical School in 2002, and has been focusing on the research fields of neuroimmunology and basic immunology. His early work contributed to the clarification of the pathogenic roles of anti-AQP4 antibody in NMOSD by applying both in vitro and in vivo models. After the series of work related to mucosal immunity and autoimmune dysregulation, the current primary interest has been focused on identifying the comprehensive network of immune responses by applying transcriptome analysis in autoimmune diseases.

Abstract of Lecture:

Dysregulation of immune responses is the hallmark of peripheral immunity in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). In this regard, the comprehensive understanding of immune signature is crucial to have deeper and previously unrecognized insight of the NMOSD pathogenesis. Transcriptome analysis conducted by RNA-seq methods is a powerful tool to detect both comprehensive and interactive responses of various types of immune subsets. In the lecture, the recent advance of our understanding related to NMOSD patients is presented from our findings of novel role of peripheral neutrophils and disease activity marker.

Letizia Leocani is Associate Professor in Neurology at University Vita-Salute San Raffaele in Milan, President Elect of the Italian Society of Clinical Neurophysiology and Vice-Chair of the Medical Devices EMA Expert Panel subgroup for the central and peripheral nervous system.

She specialized in Neurology after being Research Fellow at the Human Motor Control Section of the National Institutes of Health in Bethesda, USA, during her PhD in Human Physiology. Her research focuses on developing and implementing innovative technologies to study the visual, cognitive and movement functions and to diagnose, monitor and treat pathological dysfunctions: from digital sensors to recording the electrical activity of the brain, to non-invasive neurostimulation. Prof Leocani coordinated several scientific studies and is in the editorial board of several international journals. She is executive board member of several scientific organizations such as Italian society of Neurology, European Academy of Neurology, RIMS-rehabilitation in Multiple Sclerosis. She is also Clinical Ambassador and Mentor for the European Institute of Innovation & Technology (EIT).

Abstract of Lecture 1:

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques widely explored as a potential treatment in several neuropsychiatric disorders. While rTMS is routinely used as a therapeutic intervention for major depression and obsessive-compulsive disorder not responsive to a first pharmacologic treatment, several evidence points to an additional use of non invasive brain stimulation, based on the possibility to enhance brain plasticity and thus potentiate the effects of rehabilitation. Several studies point to the benefits of combining rehabilitation – physical, cognitive – with non invasive brain stimulation in movement disorders, stroke, multiple sclerosis and neurodegenerative dementing diseases. Further randomized, controlled studies are needed to strengthen this evidence and provide information about the criteria to identify the modalities of administration in terms of dosing, schedule and brain target, and to identify the best potential responders.

Abstract of Lecture 2:

Preclinical evidence points to the potential beneficial effects of neuronal activity on (re-)myelination during development and in demyelinating diseases. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation (NIBS) techniques widely explored as a potential treatment in several neuropsychiatric disorders. Repetitive TMS is routinely used for the treatment of major depression and obsessive-compulsive disorder not responsive to a first pharmacologic treatment. More recent studies proposed to profit of the benefits of combining rehabilitation – physical, cognitive – with non-invasive brain stimulation in movement disorders, stroke, multiple sclerosis and neurodegenerative dementing diseases. In most neurological diseases, neurons are the main target of NIBS for promoting their survival and plasticity of synaptic connections. In Multiple Sclerosis, two additional targets for NIBS are represented by the immune and myelination mechanisms, which may be modulated directly, or indirectly by changes in neuronal activity and polarization.

Dr Jennifer Massey MBBS (Hon) FRACP PhD Staff Specialist Neurologist SVHNS, MS Research Australia Post-Doctorate Fellow, Senior Lecturer UNSW School of Clinical Medicine

Jennifer Massey is a consultant neurologist with a specialist interest in neuroimmunology and MS. She graduated from University of Western Australia with honours in 2009, completing neurology specialty training in 2018. In 2021 Dr Massey completed her PhD in immune reconstitution therapies for MS. Jennifer currently works across the St Vincent’s Health Campus in Sydney, including her role as the lead neurologist in the ongoing AHSCT for MS and other Neuroimmunological Disease trials and is a co-investigator on other MS clinical trials. She remains active in translational research with a recent successful NHMRC grant to investigate the role of EBV in MS, and has published extensively in MS immunopathology.

Jennifer remains passionate about the care of patients with MS.

Abstract of Lecture:

Interest in the role of Epstein Barr Virus (EBV) in multiple sclerosis has intensified based on strong epidemiological evidence of an association between EBV seroprevalence and MS. Hypotheses proposed to explain the biological relationship between EBV and MS include molecular mimicry, EBV immortalised autoreactive B cells and infection of glial cells by EBV.

Examining the interaction between EBV and immunotherapies that have demonstrated efficacy in MS offers clues to the validity of these hypotheses. The efficacy of B cell depleting therapies could be consistent with a hypothesis that EBV-infected B cells drive MS; however, loss of T cell control of B cells does not exacerbate MS. A number of MS therapies invoke change in EBV-specific T cell populations, but public/shared pathogenic EBV-specific T cells with cross-reactivity to CNS antigen remain elusive. Immune reconstitution therapies induce EBV viraemia and expansion of EBV-specific T cell clones, but this does not correlate with relapse. Much remains unknown regarding the role of EBV in MS pathogenesis. This talk will review the current field and explore important knowledge gaps.

Meaghan Osborne is currently a Neurology and Stroke Nurse Practitioner at the Royal Brisbane and Women’s Hospital. She completed her Masters of Nursing, Nurse Practitioner at the University of Newcastle and is the current president of Multiple Sclerosis Nurses Australasia. Previously Meaghan has worked in the Neuroscience clinical area; Stroke, Neurosurgery and Neurology and has specialised in the area of Multiple Sclerosis and Stroke nursing. In particular, she has specialised in high efficacy therapy for treatment of MS. Meaghan has a keen interest in standards of care in nursing and the deteriorating neuroscience patient. As a nurse practitioner she aims to improve the quality of life of MS patients and deliver expert, holistic, patient centred care across continuum.

Abstract of Lecture:

The Multiple Sclerosis Nursing role is integral to the care of the person with MS. The MS Nurse practitioner is an advanced practice provider that provides comprehensive care to MS patients across the continuum. It includes assessment and management using nursing knowledge and skills. The role may include, but is not limited to, the direct referral of patients to other healthcare professionals, prescribing medications, ordering, and interpreting diagnostic investigations. It is grounded in the nursing profession’s values, knowledge, theories, and practice, and provides innovative and flexible health care delivery that complements other health care providers.

The Nurse Practitioner practice is embedded in the nursing profession and provides holistic care to MS patients and their families. This session will highlight the strengths of the MS nurse practitioner and MS, whilst providing practical examples of its implementation during family planning and caring for the woman with MS post-partum.

A/Prof Palendira heads the Human Immunology laboratory at the University of Sydney. Having trained under Prof Alan Rickinson on EBV immunobiology, Palendira played a critical role in establishing the molecular pathogenesis of EBV infection in primary immunodeficiencies such as X-linked lymphoproliferative disease. His expertise includes cellular immunology, EBV immunobiology and immune profiling of human tissues. Palendira leads a multi-disciplinary team that focusses on how the human immune system deals with viral infections and cancers. The team is at the forefront of developing methodologies and protocols for mapping immune responses in clinical specimen that are currently being used by many clinical laboratories, including for monitoring clinical trial outcomes. His team has also developed and published analyses pipeline for high-dimensional data sets, including mass cytometry data analysis, cellular neighbourhood analysis, mapping cellular interactions within tissues and quantitative analysis of multi-parameter data sets. Palendira has published 64 high-impact publications in international journals such as Nature, Cancer Cell and Clinical Cancer Research and has secured over 15 million dollars in peer-reviewed competitive grant funding.

Abstract of Lecture:

Epstein-Barr virus (EBV) is perhaps one of the most successful pathogens to infect humans. With over 90% of the population sero-positive for this virus and lifelong persistence in the infected host, EBV defines one of the most successful host-pathogen interactions known to mankind. However, EBV is also the first human oncogenic virus to be identified and thus far has been implicated in at least 7 different types of malignancies in human. There is mounting evidence implicating EBV in the development of MS. Risk of developing MS is extremely low in uninfected individuals, however, a history of symptomatic primary infection and elevated antibody responses to EBV significantly increase the risk of MS. There are, however, many questions that remain unanswered, and the underlying mechanism is far from clear. In this talk I will provide a summary of all the evidence we have on the role of EBV in MS, show where there are still gaps in our understanding and discuss the future directions.

Dr. Sasitorn Siritho is one of the renowned neurologists in Bangkok, Thailand. She has 20 years of experience in her field. Her specialized focus encompasses multiple sclerosis and related disorders. She holds a medical doctorate and is an alumna of the Faculty of Medicine at Siriraj Hospital, Mahidol University, Thailand.

Her career is marked by noteworthy achievements, including earning her diploma from the Thai Board of Internal Medicine in 1999 and subsequently from the Thai Board of Neurology in 2005. Her pursuit of excellence led her to complete a stroke fellowship at the National Stroke Research Institute, Australia, in 2003. Moreover, in 2008, she secured a multiple sclerosis fellowship from the University of Ottawa, Canada. She is now the Thai MS Society's Chairman and the Siriraj Neuroimmunology Center's head. She is the author of over 80 publications and has been involved in more than 70 peer reviews.

Abstract of Lecture:

Multiple sclerosis (MS) is a multifaceted central nervous system disease characterized by inflammation, autoimmunity, and demyelination. The disease's intricate pathogenesis involves an initial phase of neuroinflammation followed by secondary neurodegeneration.

Extensive research emphasizes the importance of early intervention in the "window of opportunity" to mitigate irreversible damage. High-efficacy disease-modifying drugs (DMDs) have garnered substantial evidence supporting their use for long-term positive outcomes. The landscape of MS treatment is swiftly evolving, with numerous DMDs available. However, there exists a need for more head-to-head comparative data among these drugs, along with a lack of clearly defined biomarkers to guide treatment effectiveness and disease progression.

Selecting the most suitable DMD demands careful consideration of factors such as the type of MS, disease activity, progression patterns, and potential side effects. During the decision-making process, it's vital to weigh the underlying aspects of the patient's condition alongside the anticipated impacts of the chosen DMD. We will illustrate some cases during the discussion.

Dr. Su-Hyun Kim presently holds the position of a neurologist within the Department of Neurology at the National Cancer Center, Goyang, South Korea. Her association with this institution dates back to 2013. Dr. Kim’s journey into the medical field began when she earned her medical degree in 2004 at Gachon University of Medicine and Science in Incheon, South Korea. She completed her residency at Gil Medical Center, also situated in Incheon, in the year 2009. It was during this time that she also attained her master’s degree from Gachon University of Medicine and Science. From 2009 to 2013, Dr. Kim pursued specialized training through fellowships in neuromuscular disorders at Seoul National University Hospital, as well as in neuroimmunology at the National Cancer Center. This period of focused study enriched her expertise in these areas. In 2017, her educational journey culminated in the achievement of a doctorate from Gachon University of Medicine and Science. Dr. Kim’s professional accomplishments extend beyond her academic pursuits. In the year 2013, she was the recipient of esteemed awards that celebrated her contributions as a young researcher. Notably, she received both the Hang-Sul award and the 5th LG Future medical scientist award. Within the realm of research, Dr. Kim had been prolific, delving into topics such as multiple sclerosis, neuromyelitis optica and neurological complications among cancer patients. Her work has led to numerous publications, contributing to the advancement of knowledge in these field. In addition to her existing acheivement, Dr. Kim has taken of the role of Scientific Committee member of PACTRIMS and the Education Director of the Korean Society of Neuroimmunoloy since 2022.

Abstract of Lecture:

Over the years, significant progress in understanding the underlying mehanisms of multiple sclerosis (MS) pathogenesis had led to introduction of an arsenal of disease-modifying therapies (DMT) that has provided neurologists more options for treating MS, improving neurological outcomes. Recent clinical studies have demonstrated the benefits of initiating highly effective DMT at an earlier stage of MS. Even with accurate early diagnosis, aggressive treatment, and vigilant clinical and paraclinical monitoring for breakthrough disease activity, a proportion of MS patients inevitably accumulate neurological disability and transition into a progressive disease course. The need for treatments that can stop or slow progression or improve disability in progressive forms of MS is even higher. Safety, tolerability, adherence, and possibly severe side effects are still unmet needs. Given this, more targeted and effective immunotherapies that restore self-tolerance, thereby reinstating the immune balance without causing general immune suppression, may hold promise for the treatment of MS. Furthermore, advancements in neuroprotective and remyelination therapies can offer new horizons for preventing long-term disability in MS patients. The future of MS treatment strategies lies in the convergence of personalized immunomodulation, neuroprotection, remyelination therapies, and combination therapies.

Mitsuru Watanabe, MD, PhD, is an Assistant Professor in the Department of Neurology at Kyushu University Hospital, Fukuoka, Japan. Dr. Watanabe obtained his medical degree from Kyushu University in 2006, started his academic carrier at Graduate School of Medical Sciences, Kyushu University since 2012, and received his Ph.D. in 2017 from Kyushu University. He was awarded the Investigator Award at 11th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) in 2018. His research interests focus on fluid biomarkers and epidemiology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). He is a member of the Japanese Society for Neurology and a councilor of the Japanese Society for Neuroimmunology.

Abstract of Lecture:

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system. In clinical practice, disease activity is mainly assessed by clinical evaluation and neuroimaging. However, more sensitive biomarkers reflecting disease activity are needed to improve the prognosis. The levels of neurofilament light chain (NfL), one of three types of neuronal intermediate filament, elevate upon neuroaxonal damage not only in cerebrospinal fluid but also in blood. In MS, many studies showed that blood NfL can be a good biomarker representing disease activity, treatment response and prognosis. Therefore, blood NfL is expected to be used in daily clinical practice in the future to monitor disease activity and predict prognosis in each individual. Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy mediated by anti-aquaporin 4 antibody that typically presents with severe and recurrent attacks in the optic nerve and spinal cord. Glial fibrillary acidic protein (GFAP), an intermediate filament of astrocytes, in blood is reported to be associated with disease activity and disability in NMOSD. This lecture provides updates on biofluid biomarkers including NfL and GFAP in MS and NMOSD and discuss whether they can be applied to clinical practice.

Professor Wiendl studied medicine in Germany, Switzerland, and the USA, graduating in 1996. After working as a research fellow at the Institute of Neuroanatomy, Nuremberg, and the Max Planck Institute for Neurobiology and the Department of Neurology, Tuebingen, he became head of the clinical research group for multiple sclerosis (MS) in Wuerzburg in 2005 and acted as a vice-chair of the Department of Neurology. In 2010, he was recruited to Muenster University Hospital as director of the Department of Neurology – Inflammatory Disorders of the Nervous System and Neurooncology. Since 2013, he serves as head of the Department of Neurology, Muenster – to which the Institute of Translational Neurology has been associated since 2018. His research focusses on inflammatory neurodegeneration and immune regulation and protection as well as monitoring MS and its therapy. His achievements have been recognized by both Sobek awards of the German Society for MS (DMSG) (2004; 2015). In 2017, Heinz Wiendl was appointed Honorary Professor at Sydney Medical School. Masshad University awarded him the title of Honorary Doctor and Honorary Professor in 2021.

Professor Wiendl is a member of numerous scientific and academic advisory boards and expert panels, including editorial boards of international scientific journals in the fields of neurology, neurosciences, and immunology, as well as for societies, foundations, and project promoters. Currently, he is the speaker of the Collaborative Research Center 128 "Multiple Sclerosis", and speaker of the competence network Multiple Sclerosis (KKNMS). Furthermore, he was appointed fellow of the American and the European Academy of Neurology in 2019. Until 2016, Heinz Wiendl was Vice Dean for Research of the Medical Faculty in Muenster. He is founder and principal investigator of the "Body and Brain Institute" Muenster, a prestigious research building funded by the German Federal Ministry.

Professor Wiendl served as a PI for or coordinated through membership of steering committees ≥40 phase I-IV clinical trials. Since 1998, he has authored more than 600 peer-reviewed publications in high-impact journals such as Nature Medicine, Journal of Experimental Medicine, Blood, Annals of Neurology, BRAIN, Neurology, Nature Neuroscience, Immunity (H index = 73, approx. 1,500 citations/year), 4 books (editor), several book chapters.

Abstract of Lecture:

EBV has been accused to be involved in the tissue mechanisms to unravel clinical multiple sclerosis and pathogenic concepts consider EBV persistence a mechanism potentially propagating MS disease progression. Our work intended to define unsupervised immunological signatures associated to the disease, looking at different compartments, hence discovered that there is a broader T cell receptor repertoire against EBV in MS patients. Our work investigates a large number of MS patients, controls, and monozygotic twin pairs discordant for multiple sclerosis and includes the assessment of different compartments (peripheral blood, cerebrospinal fluid). Following the notion that CSF also contains EBV-specific central neural CD8 cells, suggesting recent finding, MS is not only preceded by EBV infection, but also associated with a broader EBV repertoire and this is consistent with an ongoing EBV immune alteration in MS. Further data show the response of EBV-specific T cell receptor repertoire by therapeutic modification, particularly treatment with CD20-depleting antibodies.

Kazuo Fujihara, M.D. is Professor, Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, and Director, Multiple Sclerosis & Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience (STRINS), Koriyama, Japan. Dr. Fujihara has served as a member of International Panels on diagnoses of MS (2010 and 2017), NMOSD (2015) and MOGAD (2023). He is an inaugural member and President (2018~) of Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), Immediate Past President (2019~2022) of Japanese Society for Neuroimmunology (JSNI), and Honorary Member of The Association of Sri Lankan Neurologists (2012~), Indian Academy of Neurology (2015~) and Hong Kong Society of Multiple Sclerosis (2015~), and Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) (2023~)

Abstract of Lecture:

Clinical disability in progressive MS (PMS) progresses independently of relapse activity and the pathogenesis of PMS is a complex, multifactorial process including neurodegeneration. Thus, PMS is difficult to treat and in fact, the efficacy of approved anti-inflammatory drugs for PMS, such as ocrelizumab and siponimod, is limited. Younger patients with shorter duration of PMS and more active disease at baseline appear to benefit the most from the available treatments. But other modes of therapy including drugs with neuroprotective or remyelinating effects, stem cell transplantation and other types of cell therapy, etc are also being evaluated in PMS. In a recent position paper, European experts recommended making treatment decisions in PMS based on the individual patient's pattern of disease progression, as well as functional, clinical and imaging parameters, rather than on their clinical phenotype. In this presentation, therapeutic evidences of PMS, novel therapies and the challenges in research and clinical practice will be discussed.

Dr Lekha Pandit is a professor of Neurology and Director of Centre for Advanced Neurological Research, at Nitte University, Mangalore, India. Her clinical and research interests include observational studies , including treatment effects in patients with MS, MOGAD, NMOSD and seronegative disease, diagnostic assays and biomarkers, genetic and environmental associations. She has authored over 175 publications in peer reviewed journals and has contributed 16 chapters . Dr Pandit has been a recipient of the Fulbright-Nehru fellowship and is an awardee of the National Academy of Science ,India. She has a special interest in supporting access to care in resource-poor settings and is associated with the MS International Federation’s (MSIF) access to care efforts. She is the current secretary of PACTRIMS

Abstract of Lecture:

The International MOGAD panel proposed diagnostic criteria was published earlier this year. In the first instance, clinical phenotypes known to be associated with MOGAD were listed - optic neuritis, myelitis, ADEM, brainstem/cerebellar dysfunction, symptomatic brain disease or a combination. There are clinical and MRI supportive features that may be used to support clinical diagnosis. At the core of this criteria is the testing and interpretation of MOG-IgG assays. Despite the fulfillment of these criteria, alternate causes need to be excluded. This talk will focus on all aspects of this criteria using illustrative cases.