Program

Executive Summary：
Samuel F. Berkovic AC, MD, FAA, FRACP, FAHMS, FRS

Sam Berkovic is Laureate Professor in the Department of Medicine, University of Melbourne. He is a clinical neurologist and clinical researcher with strong basic science collaborations. His group, together with molecular genetic collaborators in Adelaide and Germany, discovered the first epilepsy gene in 1995 and subsequently have been involved the discovery of many of the known epilepsy genes. This has changed the conceptualisation of the causes of epilepsy and is having a major impact on epilepsy research, and on strategies for diagnosis and development of new treatments. Currently he a co-PI on “Epi25” a major NIH funded project to sequence 25,000 epilepsy genomes and he heads the ILAE Consortium on Complex Epilepsies. He was elected a Fellow of the Royal Society (London) in 2007.

Lecture Abstract：
Progressive Myoclonic Epilepsies in the Asian-Oceanic region:
from History, Classification to Genetics

Samuel F Berkovic
University of Melbourne

Progressive myoclonus epilepsy (PME) is a rare epilepsy syndrome essentially always due to a genetic causes. Diagnosis used to be based on pathological features, if a diagnosis in life could be made, but now advances in genetics have allowed rapid and accurate categorization of cases. There are now over 40 recognised genetic causes of PME. Recessive, dominant, and mitochondrial causes are known and there appears to be regional variation in the pattern of underlying disorders. Unverricht-Lundborg disease and Lafora disease are the most common causes of PME in European populations, but appear to be less prevalent in Asia, although both have been described. In contrast, sialidosis seems relatively more prevalent in Taiwan and dentatorubral-pallidoluysian atrophy shows a concentration of cases in Japan.

Familial adult myoclonic epilepsy (FAME), which clinically overlaps with PME, has recently been intensively studied and clarified at a molecular level by international studies, but particularly by research in the Asian region. FAME clinically lies between the idiopathic generalised epilepsies and PME. A key feature is very prominent tremor which neurophysiologically is cortical myoclonus. FAME is associated with very slow progression and thus can present as a PME. Inheritance is autosomal dominant with high penetrance. The molecular basis remained mysterious until Japanese researchers found an unusual mechanism – an expanded pentanucleotide repeat. Now seven loci are known in different genes, each with similar expanded repeat motifs leading to the FAME phenotype.

High quality research in the Asian Oceanian region has contributed to the clinical, neurophysiological and now genetic dissection of this fascinating group of epilepsies.

Executive Summary：
Akio IKEDA, MD, PhD, FACNS is currently Professor, Department of Epilepsy, Movement Disorders and Physiology at Kyoto University School of
He was appointed as the Regional Chair of ILAE-Asia Oceania (2017-2021) and the President of JES (2017-2021), currently being past-chair and vice president. He was trained in Epilepsy and Clinical Neurophysiology in Cleveland Clinic Foundation, Ohio, USA between 1989 and 1991, and earned his PhD from Kyoto University in 1993.

Dr. IKEDA is involved in clinical epilepsy, neurology, and clinical neurophysiology, including epilepsy surgery (i.e., epileptogenesis made by astrocytes, ictal DC shifts. wide-band EEG), central control of myoclonus, motor seizures, movement disorders, and voluntary movements by slow cortical potentials (Bereitschaftspotentials and CNV). Currently also scalp-recorded infraslow activity as the causative EEG biomarker candidates in various neurological disorders aiming at CSD (cortical spreading depolarization) (migraine, amyloid spell, transient focal neurological episodes, head trauma, critical care, etc.). He has been working on clinical pathophysiology and treatment of BAFME (Cortical Tremor) since 1990 (Neurology,40:1561-1565)
He was an Associate Editor of Epilepsia (2013-2017) and Neurology & Clinical Neuroscience (2013-2018) (English journal of Japan Neurology Society) and sits on the editorial boards of many journals.
He has published in the literature having authored more than 480 original articles (385 in English, 95 in Japanese), 360 review articles (30 in English, 330 in Japanese), 182 book chapters (17 in English, 165 in Japanese) and 13 books (1 in English, 12 in Japanese). Invited lectures were done in 185 international academia meetings, and in 260 domestic academia meeting.

Lecture Abstract：
In 1950s about 6 case reports in Japa as “familial tremor with seizure” for nationwidely, and later many terms were utilized for this unique disease such as Benign myoclonus epilepsy (1986), Familial essential myoclonus and epilepsy (FEME) (1990), cortical tremor (1990), Familial adult myoclonic epilepsy (FAME) (1985), Benign adult onset familial myoclonus epilepsy (BAFME).
In early 1990s, main clinical features of this disease (BAFME/FAME) were crystalized as follows; 1) located in Japan and Europe, 2) autosomal dominant inheritance of high penetrance, 3) middle age onset of finger tremor, later rare generalized seizure, 4) no cerebellar or intellectual problems, 5) over 60 years their symptoms became worse, 6) clinical anticipation occurs. 7) Finger tremor was cortical myoclonus (giant SEPs, Jerk-locked averaging, C-reflex). 8) EEG shows generalized spike and wave complexes of >3Hz and occipital spike, 9) photosensitivity. Taking all into account, either Indiopathic Generalized Epilepsy with prominent finger cortical myoclonus, or late onset benign type of Progressive Myoclonus Epilepsy (PME) was speculated in the latter1990s.
Unsolved questions remained in 2000s as follows; 10) why it is tremulous contrary to usual cortical myoclonus ?, 11) any EEG biomarker ? 12) ageing or degeneration aggravate symptoms? Once expanded repeat (TTTTA/ TTTCA) at intron was discovered in 2018, disease schema began to be solved. Recent neurophysiological achievement also solved the mysteries of 10-12) by new noninvasive analysis as follows.
10) Si-TiFCA (somatosensory-induced, time-frequency cortical activity analysis) revealed repetitive, alternating cortical power increases and decreases which could explain tremulousness (Yamanaka et al, in revision), 11) high frequency oscillation occurred on P25 (P25-HFO) of giant SEPs with 100% sensitivity and 88% specificity in BAFME, not other PMEs (Tojima et al.,2021), 12) positive correlation between ageing and giant SEPs were found, but the repeat number does not positively correlate to giant SEPs (Neshige et al.,2021).

Executive Summary：
Dr Meng-Han Tsai is a Professor of School of Medicine, Chang Gung University and the Director of the Department of Medical Research and Deputy Director of Department of Neurology at Kaohsiung Chang Gung Memorial Hospital. He also served as the Secretary of ILAE Genetic Commission. He is a board member of Taiwan Neurology Society, Taiwan Epilepsy Society, Taiwan Rare Neurological Disease Society, Taiwan Neuroimmunology Medicine Society and the current President of the Kaohsiung Epilepsy Association.
He acquired medical degree (MD) at Kaohsiung Medical University in 2003, completed neurology residency training at Kaohsiung Chang Gung Memorial Hospital from 2003 to 2008. In 2009, Dr. Tsai jointed the research team at Epilepsy Research Center and Florey Institute of Neuroscience and Mental Health, Melbourne, Australia. He obtained his PhD degree at University of Melbourne, Australia under the supervision of two distinguished professors, Prof. Samuel F. Berkovic, and Prof. Ingrid E. Scheffer in the field of “Genetics of Epilepsy”. After returning to Taiwan, Dr. Tsai continues his clinical and research interests in the field of epilepsy genetics. He received many research grants from Chang Gung Medical Research Found, Nation Science and Technology Council and National Health Research Institute Research Project about familial and genetic epilepsy. Dr Tsai recently identified several novel human lissencephaly genes, including CEP85L published in Neuron (IF=18.3), NDEL1 published in Acta Neuropathologica (IF=12.7). He also actively participates in international research collaboration, such as Epi25K consortium, ILAE GWAS Consortium, EpiNet, the research task force of Commission on Asian and Oceanic Affairs (CAOA) and Genetic Commission of ILAE. He also has research collaboration with Australia, Germany, Canada, Italy, UK and Malaysia.
Dr. Tsai has received several research awards and travel grants from Taiwan Neurology Society, Epilepsy Society of Australia, and Taiwan Epilepsy Society, American Epilepsy Society and International League against Epilepsy, including the GSK Epilepsy Research Award of Taiwan Epilepsy Society in 2014 and 2021.

Lecture Abstract：
Familial Adult Myoclonic Epilepsy Type 1 (FAME1) is an autosomal dominant disorder characterized by adult-onset cortical tremor, myoclonus, and infrequent epilepsy, following a slowly progressive course. The genetic cause of FAME1 was identified in 2018 by Ishiura et al., who discovered a complex pentanucleotide repeat expansion (TTTTA) and an insertion (TTTCA) in the intron of the SAMD12 gene.
Since this discovery, eight types of FAME (FAME1-FAME8) have been reported. Notably, FAME1 has been identified in families from Japan, China, Thailand, Sri Lanka, India, and even in individuals of European descent residing in Canada. In contrast, FAME2 and FAME3 are predominantly observed in Caucasian populations.
The genetic diagnosis of FAME poses significant challenges due to the large repeat expansion size and the complex motif structure. In this talk, I will discuss recent advancements in genetic testing for FAME and provide an overview of its treatment options.