261
-シン ポジ ウム
S-03-2
Update on Tremor
Department of Neurology, Kitasato University School of Medicine
○Ritsuko Hanajima
Tremor is the most common involuntary movement, defined as an involuntary rhythmic oscillation of some body part. The classification of tremor is based on clinical characters, such as activation conditions (rest, or action) and tremor frequency. The Consensus Statement of the Movement Disorder Society on Tremor was proposed in 1998. The tremor classification should be updated based on several factors concerning it, such as genetic factor, physiologic characters, pathophysiology, clinical features or others. In 2015, Gövert and Deuschel suggested that the essential tremor is not produced by a single etiology and but is originated from heterogeneous etiologies, and that
"dystonic tremor" may be underestimated as compared with a real occurrence rate.
Several pathophysiological mechanisms must produce an oscillatory movement of tremor, but they are still unclear.
Both of peripheral and central mechanisms were known to generate tremor rhythms.
《Curriculum Vitae》
Education and Training
Yokohama City University, School of Medicine: MD The University of Tokyo, Graduate School of Medicine: Ph.D.
Junior Resident: Toranomon Hospital
Clinical Fellow: The University of Tokyo Hospital Professional Experience
Jan 2001～December 2003
Research Fellow: Toronto Western Hospital, the University of Toronto Dec 2003～April 2007
Project Research Associate of “21th century COE program “Center for Integrated Brain Medical Science” : Department of Neurology, University of Tokyo Hospital
May 2007～March 2014
Assistant Professor: Department of Neurology, the University of Tokyo Hospital,
March 2014～Presence
Lecturer:: Department of Neurology, Kitasato University School of Medicine,
Editorial board: Clinical neurophysiology, Brain stimulation.
S-03-3
What’s Dystonic tremor?
Fukushima Medical University
○Yoshikazu Ugawa
Considerable numbers of patients with dystonia also have oscillatory involuntary movements which are considered to be a kind of tremor because of their oscillatory character. These oscillations have been theoretically classified into two kinds:dystonic tremor (DT)andtremor associated with dystonia (TAD)based on clinical features. DT is defined as tremor in an extremity or body part that is affected by dystonia and often stopped by sensory trick, and TAD as tremor occurring in a body part not affected by dystonia, but the patient has dystonia elsewhere. Another embarrassing factor on this issue is that some patients with dystonia gene have oscillatory movements usually called as tremor.
These oscillations have been physiologically classified into two kinds:rhythmic jerky movements (J)and nearlysinusoidal movements (SM). The former is often associated with dystonia, especially in the neck, and may be produced by the similar mechanism underlying dystonia. It is sometimes considered to a kind of myoclonus. The latter may be produced by some oscillator mechanism in basal ganglia, which may be the same generator for some tremor. Clinical DT includes both J and SM. DAT also includes both of them. However, DT sometimes has only J in which case the dystonic mechanism alone may explain the symptoms. TAD more often has SM alone as compared with DT.
My conclusion: Most of dystonic tremor is a kind of dystonia. Dystonic tremor may be rhythmic jerky movements often seen in dystonia. Other associated sinusoidal movements may be a kind of tremor probably generated by ET lime mechanisms. The most important point we should care is that some patients with dystonic tremor show only jerky tremulous movements without apparent dystonia. Clinically distinct DT and TAD should consist of physiologically different two movements. The ratio of two movements must be different between the two clinically defined tremors.
《Curriculum Vitae》
PROFESSIONAL EXPERIENCE
1978-2007 Department of Neurology, the University of Tokyo
(July, 1987 - December, 1989 study under Professor Marsden at the Institute of Neurology, Queen Square, London) May, 2007- present Professor and Chairman, Department of Neurology School of
Medicine, Fukushima Medical University
April 2012- Vice president of Fukushima Medical University Hospital MEMBERSHIPS
International Federation of Clinical Neurophysiology (IFCN)
Secretary of International Federation of Clinical Neurophysiology (IFCN) 2014-2017 Movement Disorders Society
Asian Oceania Section of the movement disorders society Executive committee, treasurer 2013 -2015 Japanese Society of Neurology executive board members Japanese Society of Clinical Neurophysiology executive board members Movement disorders society, Japan executive board members President elect 2015－2017 Editorial Boards
Clinical Neurophysiology Editorial board (2003/03 Associate editor (2006/07 -Movement disorders (2006/02-2009)
The cerebellum
(2007-Frontiers in integrative physiology 2011～
Frontiers in human neuroscience 2012～ and others
シンポジウム S-03：Movement disorders update
5月18日（水） 13：15～15：15 第11会場(神戸国際会議場3・4F 国際会議室)
シン ポジ ウム
S-03-2
Update on Tremor
Department of Neurology, Kitasato University School of Medicine
○Ritsuko Hanajima
Tremor is the most common involuntary movement, defined as an involuntary rhythmic oscillation of some body part. The classification of tremor is based on clinical characters, such as activation conditions (rest, or action) and tremor frequency. The Consensus Statement of the Movement Disorder Society on Tremor was proposed in 1998. The tremor classification should be updated based on several factors concerning it, such as genetic factor, physiologic characters, pathophysiology, clinical features or others. In 2015, Gövert and Deuschel suggested that the essential tremor is not produced by a single etiology and but is originated from heterogeneous etiologies, and that
"dystonic tremor" may be underestimated as compared with a real occurrence rate.
Several pathophysiological mechanisms must produce an oscillatory movement of tremor, but they are still unclear.
Both of peripheral and central mechanisms were known to generate tremor rhythms.
《Curriculum Vitae》
Education and Training
Yokohama City University, School of Medicine: MD The University of Tokyo, Graduate School of Medicine: Ph.D.
Junior Resident: Toranomon Hospital
Clinical Fellow: The University of Tokyo Hospital Professional Experience
Jan 2001～December 2003
Research Fellow: Toronto Western Hospital, the University of Toronto Dec 2003～April 2007
Project Research Associate of “21th century COE program “Center for Integrated Brain Medical Science” : Department of Neurology, University of Tokyo Hospital
May 2007～March 2014
Assistant Professor: Department of Neurology, the University of Tokyo Hospital,
March 2014～Presence
Lecturer:: Department of Neurology, Kitasato University School of Medicine,
Editorial board: Clinical neurophysiology, Brain stimulation.
S-03-3
What’s Dystonic tremor?
Fukushima Medical University
○Yoshikazu Ugawa
Considerable numbers of patients with dystonia also have oscillatory involuntary movements which are considered to be a kind of tremor because of their oscillatory character. These oscillations have been theoretically classified into two kinds:dystonic tremor (DT)andtremor associated with dystonia (TAD)based on clinical features. DT is defined as tremor in an extremity or body part that is affected by dystonia and often stopped by sensory trick, and TAD as tremor occurring in a body part not affected by dystonia, but the patient has dystonia elsewhere. Another embarrassing factor on this issue is that some patients with dystonia gene have oscillatory movements usually called as tremor.
These oscillations have been physiologically classified into two kinds:rhythmic jerky movements (J)and nearlysinusoidal movements (SM). The former is often associated with dystonia, especially in the neck, and may be produced by the similar mechanism underlying dystonia. It is sometimes considered to a kind of myoclonus. The latter may be produced by some oscillator mechanism in basal ganglia, which may be the same generator for some tremor. Clinical DT includes both J and SM. DAT also includes both of them. However, DT sometimes has only J in which case the dystonic mechanism alone may explain the symptoms. TAD more often has SM alone as compared with DT.
My conclusion: Most of dystonic tremor is a kind of dystonia. Dystonic tremor may be rhythmic jerky movements often seen in dystonia. Other associated sinusoidal movements may be a kind of tremor probably generated by ET lime mechanisms. The most important point we should care is that some patients with dystonic tremor show only jerky tremulous movements without apparent dystonia. Clinically distinct DT and TAD should consist of physiologically different two movements. The ratio of two movements must be different between the two clinically defined tremors.
《Curriculum Vitae》
PROFESSIONAL EXPERIENCE
1978-2007 Department of Neurology, the University of Tokyo
(July, 1987 - December, 1989 study under Professor Marsden at the Institute of Neurology, Queen Square, London) May, 2007- present Professor and Chairman, Department of Neurology School of
Medicine, Fukushima Medical University
April 2012- Vice president of Fukushima Medical University Hospital MEMBERSHIPS
International Federation of Clinical Neurophysiology (IFCN)
Secretary of International Federation of Clinical Neurophysiology (IFCN) 2014-2017 Movement Disorders Society
Asian Oceania Section of the movement disorders society Executive committee, treasurer 2013 -2015 Japanese Society of Neurology executive board members Japanese Society of Clinical Neurophysiology executive board members Movement disorders society, Japan executive board members President elect 2015－2017 Editorial Boards
Clinical Neurophysiology Editorial board (2003/03 Associate editor (2006/07 -Movement disorders (2006/02-2009)
The cerebellum
(2007-Frontiers in integrative physiology 2011～
Frontiers in human neuroscience 2012～ and others
シンポジウム S-03：Movement disorders update
5月18日（水） 13：15～15：15 第11会場(神戸国際会議場3・4F 国際会議室)
262 -シン
ポジ ウム
S-03-4
Huntington’s disease-update
Department of Neurology, National Hospital Organization, Sagamihara National Hospital
○Kazuko Hasegawa
Huntington’ s disease (HD) was known as Huntington’ s chorea for a long time, because it was published as "on Chorea"
by George Huntington in 1872. Because chorea is just one of the manifested symptoms of this disease, it is more appropriate to be called as HD since 1998. HD is one of the rare intractable neurodegenerative disorders, of which clinical hallmark is both of abnormal movements and psychiatric manifestations. A peak age of onset is around 4thdecade, and prevalence rate is similar between female and male.
Estimated prevalence rate of HD is 0.7/100,000 and estimated less than 1000 in Japan, which is only 1/10 that of Caucasian people. Cause of this difference is reported as different frequency of haplotypes. Moreover, recent advances for modifier genes for clinical onset of HD is reported. However, the modifier genes for the variety of age of onset and disease severity among Japanese patients, most of the patient show the similar number of CAG repeats as around 45, however, have not detected yet.
Gene product is huntingtin. The function of huntingtin is not clear now, although huntingtin is widely expressed in whole body.
Symptomatic therapy is available for HD: tetrabenazine and neuroleptics for chorea, neuroleptics (typical and atypical) for psychiatric symptoms, selective serotonin re-uptake inhibitors (SSRI) and tricyclic antidepressant for depression, SSRI for impulsive compulsive disorders, rehabilitations, helmet, nutritional care and so on). No causal therapy is developed now unfortunately.
Mean duration of illness is estimated 15～20years same as Caucasians. Most of HD cases are under home care or long term hospitalization. Only a few patients are at work. Disturbed factors to work are both of psychiatric and movement disorders, especially impairment of discrete movement. Most patients are isolated from social network even from their family and friends because of their psychiatric symptoms and their heredity.
《Curriculum Vitae》
1977 : graduated Kitasato University school of Medicine 1986 : lecturer in Neurology at the Kitasato University 2001 : head of Neurology, NHO, Sagamihara Hospital
2015 : chief of laboratory for intractable neurological disease, NHO, Sagamihara Hospital
シンポジウム S-03：Movement disorders update
5月18日（水） 13：15～15：15 第11会場(神戸国際会議場3・4F 国際会議室)
263
-シン ポジ ウム
Chairs：
Hirofumi Maruyama(Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences)
Masahisa Katsuno(Department of Neurology, Nagoya University Graduate School of Medicine)
≪Objective≫
Motor neuron disease (MND), especially amyotrophic lateral sclerosis (ALS), is intractable and there is no fundamental therapy, prevention or reliable biomarkers.
Many promising therapeutic research were investigated using animal models of MND. However, they have yielded disappointing results in clinical trials. This is likely attributable to the facts that molecular and pathological changes already exist before the onset of symptoms and that there are no established biomarkers that detect the efficacy of drugs and quantify disease progression. Therefore, appropriate objective biomarkers have eagerly been awaited for MND.
Here, we focus on biomarkers of ALS and spinal and bulbar muscular atrophy, particularly their relation to disease progression. The biomarkers to be discussed include MRI, PET, nerve root sonography, oxidative stress marker, and so on. In this symposium, the leading authorities will introduce their up-to-date research on biomarkers of MND.
We hope the audience will enrich understanding and get a hint of their future research.
S-04-1
Biomarkers of Disease Progression in ALS
Eleanor and Lou Gehrig MDA/ALS Center,
Department of Neurology, Columbia University Medical Center, USA
○Hiroshi Mitsumoto
A biomarker is a measurable indicator of the severity or presence of a certain disease state. In ALS, objective and reliable biomarkers are not available. In the clinical trial setting, survival, muscle strength, ALSFRS-R, and vital capacity have been used as key outcomes. However, clinimetric measures have inherent limitations. The first step in validating biomarkers would be focusing on those that can predict natural history of disease progression. Extensive efforts have been made in the past, including neurophysiological measures (MUNE, TMS, and EIM). Some techniques have already been used in a multisite study.
Neuroimaging methods such as MR spectroscopy, PET scan detecting neuroinflammation, and cortical volumetrics show promise, yet improving sensitivity to change over time and feasibility and reliability of multisite utility requires further refinement. For biochemical markers, creatinine, from among the oldest laboratory tests, has turned out to be one of the most interesting biomarkers in ALS. It can predict survival and also demonstrates change over time (Bozik et al. 2014). Others such as uric acid, oxidative stress indicators, neurofilament subunits, and acute reactive substances require further extensive studies before they can be determined useful. A biomarker in ALS is the ’holy grail’ of our field. Every clinical trial should incorporate a biomarker study as a major component, and all investigators undertaking clinical trials and observational natural history studies, must work together to find reliable biomarkers in ALS, such as the PRO-ACT database.
《Curriculum Vitae》
Dr. Hiroshi Mitsumoto is a Wesley J. Howe Professor of Neurology at Columbia University Medical Center and has been the Director of the MDA/ALS Clinical Research Center since 1999. He was educated in Japan and trained in Internal Medicine. He graduated from Toho University School of Medicine in 1968. In 1972, he pursued further medical and neurology training at Johns Hopkins University, Case Western Reserve University, Cleveland Clinic, and Tufts University. In 1983, he began working at the Cleveland Clinic as the Director of their Neuromuscular Section and ALS Center. He has been involved with improving patient care and end of life issues in ALS for many years. He also participated extensively in clinical trials in ALS and organized several large national and international ALS Conferences. He received a number of awards, including the Forbes H. Norris Award for Compassion and Love for Humanity in Research and Treatment in Patients with ALS from the International ALS Symposium and International ALS Alliance in 1998. Dr. Mitsumoto received a number of US Federal and Foundation research grants and published many papers and books in ALS. He has been a Best Doctor in America since 1996