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Juvenile Onset Huntington's Disease • Peggy C Juvenile Onset Huntington's Disease Onset Huntington's Juvenile • Peggy • C. Nopoulos Juvenile Onset Huntington's Disease Edited by Peggy C. Nopoulos Printed Edition of the Special Issue Published in Brain Sciences www.mdpi.com/journal/brainsci Juvenile Onset Huntington’s Disease Juvenile Onset Huntington’s Disease Editor Peggy C. Nopoulos MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editor Peggy C. Nopoulos University of Iowa USA Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Actuators (ISSN 2076-0825) (available at: https://www.mdpi.com/journal/brainsci/special issues/ Juvenile Huntington Disease). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Volume Number, Page Range. ISBN 978-3-03943-811-2 (Hbk) ISBN 978-3-03943-812-9 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editor .............................................. vii Preface to ”Juvenile Onset Huntington’s Disease” .......................... ix Peg C. Nopoulos Special Issue: Juvenile Onset Huntington’s Disease Reprinted from: Brain Sci. 2020, 10, 652, doi:10.3390/brainsci10090652 ................ 1 Jordan L. Schultz and Peg C. Nopoulos Autonomic Changes in Juvenile-Onset Huntington’s Disease Reprinted from: Brain Sci. 2020, 10, 589, doi:10.3390/brainsci10090589 ................ 3 Jordan L. Schultz, Amelia D. Moser and Peg C. Nopoulos The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington’s Disease Reprinted from: Brain Sci. 2020, 10, 575, doi:10.3390/brainsci10090575 ................ 11 Kathleen E. Langbehn, Ashley M. Cochran, Ellen van der Plas, Amy L. Conrad, Eric Epping, Erin Martin, Patricia Espe-Pfeifer and Peg Nopoulos Behavioral Deficits in Juvenile Onset Huntington’s Disease Reprinted from: Brain Sci. 2020, 10, 543, doi:10.3390/brainsci10080543 ................ 19 Alexander V. Tereshchenko, Jordan L. Schultz, Ansley J. Kunnath, Joel E. Bruss, Eric A. Epping, Vincent A. Magnotta and Peg C. Nopoulos Subcortical T1-Rho MRI Abnormalities in Juvenile-Onset Huntington’s Disease Reprinted from: Brain Sci. 2020, 10, 533, doi:10.3390/brainsci10080533 ................ 31 Jannis Achenbach, Charlotte Thiels, Thomas Lucke ¨ and Carsten Saft Clinical Manifestation of Juvenile and Pediatric HD Patients: A Retrospective Case Series Reprinted from: Brain Sci. 2020, 10, 340, doi:10.3390/brainsci10060340 ................ 41 Mayke Oosterloo, Emilia K. Bijlsma, Christine de Die-Smulders and Raymund A. C. Roos Diagnosing Juvenile Huntington’s Disease: An Explorative Study among Caregivers of Affected Children Reprinted from: Brain Sci. 2020, 10, 155, doi:10.3390/brainsci10030155 ................ 59 Ashok Kumar, Vijay Kumar, Kritanjali Singh, Sukesh Kumar, You-Sam Kim, Yun-Mi Lee and Jong-Joo Kim Therapeutic Advances for Huntington’s Disease Reprinted from: Brain Sci. 2020, 10, 43, doi:10.3390/brainsci10010043 ................ 71 v About the Editor Peggy C. Nopoulos is a professor of Psychiatry, Neurology, and Pediatrics. As of 2018, Dr. Nopoulos became the first female Chair and DEO of the Department of Psychiatry at the University of Iowa Hospital & Clinics. She received her M.D. degree from the University of Iowa in 1989 and completed her postdoctoral fellowship in Neuropsychiatry. Dr. Nopoulos’ clinical and research experience in Huntington’s Disease (HD) is broad and deep. She has been providing clinical care to patients with HD as part of the HD Center of Excellence since 2003. Early in her research career, Dr. Nopoulos worked as a co-investigator in a large neuroimaging study of individuals in the pre-symptomatic phases of HD that included 32 sites around the world. In 2009, Dr. Nopoulos embarked on a unique research endeavor called Kids-HD, with the aim to address brain development in children who inherited the adult-onset form of HD. Dr. Nopoulos expanded this project in 2011 to include children with juvenile-onset HD (JOHD). The Kids-JHD study constitutes the only prospective study in the world and this work has provided novel insights into the neurobiology of JOHD. vii Preface to ”Juvenile Onset Huntington’s Disease” Receiving a diagnosis of Huntington’s Disease (HD) can be devastating for patients and families. However, the HD community has demonstrated their strength and resolve by engaging in clinical research efforts that have allowed researchers to better understand the course of HD, identify biomarkers, and investigate how various compounds impact the progression of the disease. Thanks to these efforts, the HD community has something that they have been desperately seeking for years: hope. Hope is being provided in the form of the first clinical trials aimed at slowing the progression of the disease. While these efforts are still in their infancy, simply knowing that advances are being made has provided hope to a desperate group of patients. Unfortunately, patients with Juvenile-Onset HD (JOHD) and their families may still be having trouble getting too excited about these potential therapeutic advances. There is still so much that is unknown about patients with JOHD that the HD community has been unable to make scientific advances with the same speed in this small group of patients. This book is meant to help bridge the gaps in knowledge that still remain about JOHD in an effort to provide therapeutic advances to those patients suffering from this disease. This book contains seven articles from authors around the globe who are engaging in clinical research to better understand the biology of JOHD. The information contained in this special edition represents some of the most cutting-edge information regarding JOHD. Our hope is that sharing this information will continue to broaden the HD community’s knowledge about JOHD in order to advance therapeutic development and provide the same hope to these patients that patients with HD have been given in recent years. Peggy C. Nopoulos Editor ix brain sciences Editorial Special Issue: Juvenile Onset Huntington’s Disease Peg C. Nopoulos 1,2,3 1 Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, IA 52242 USA; [email protected]; Tel.: +1-319-356-1144 2 Department of Neurology, Carver College of Medicine at the University of Iowa, Iowa City, IA 52242, USA 3 Department of Pediatrics, Carver College of Medicine at the University of Iowa, Iowa City, IA 52242, USA Received: 14 September 2020; Accepted: 14 September 2020; Published: 20 September 2020 The Special Issue “Juvenile Onset Huntington’s Disease” highlights the growing interest in understanding the unique aspects of this ultra-rare disorder. Adult Onset Huntington’s Disease (AOHD) is a single gene disorder caused by a triplet repeat expansion in the Huntingtin gene. With decades of research to support the search for a cure, we are now in an exciting time of true progress in fighting AOHD with gene therapy trials underway. However, excluded from current studies are the subset of patients who, by virtue of very high CAG repeat expansion (typically over 60), have onset of disease early in life, defined by motor onset prior to age 21 and referred to as Juvenile Onset Huntington’s Disease (JOHD). This definition is somewhat arbitrary as the pathogenic mechanism is exactly the same—expanded CAG repeat in the Huntingtin gene. Nevertheless, due to its rarity, there is a relative dearth of studies on JOHD, leaving many questions regarding its phenomenology. The current issue includes seven articles that span a variety of topics including the difficult emotional experience that parents endure in the context of their child becoming ill and diagnosed with JOHD [1]; a review of the clinical manifestations of JOHD [2]; and four articles from the only prospective study of JOHD evaluating behavior [3], the association of CAG repeat and motor onset [4], autonomic nervous system dysfunction [5], and abnormality in the unique MRI marker of T1rho in JOHD subjects [6]. Finally, this issue is rounded out by a review of the therapeutic advances for HD, highlighting the possibilities in the future of the types of clinical trials that JOHD subjects may be included in [7]. The entire HD community—patients, family members at-risk for HD, caregivers, health-care professionals and scientists—has a keen interest in focusing attention on JOHD. There is a calling to better understand, and help, the plight of those that seem to have been “left behind” in the flurry of research studies on AOHD [8]. The study of patients who are afflicted early in life with HD has become an urgent need with this Special Issue representing just the beginning of the required effort. References 1. Oosterloo, M.; Bijlsma, E.K.; Die-Smulders, C.; Roos, R.A.C. Diagnosing Juvenile Huntington’s Disease: An Explorative Study among Caregivers of Affected Children. Brain Sci. 2020, 10, 155. [CrossRef][PubMed] 2. Achenbach, J.; Thiels, C.; Lucke, T.; Saft, C. Clinical Manifestation of Juvenile and Pediatric HD Patients: A Retrospective Case Series. Brain Sci. 2020, 10, 340. [CrossRef][PubMed] 3. Langbehn, K.E.; Cochran, A.M.; van der Plas, E.; Conrad, A.L.; Epping, E.; Martin, E.; Espe-Pfeifer, P.; Nopoulos, P. Behavioral Deficits in Juvenile Onset Huntington’s Disease. Brain Sci. 2020, 10, 543. [CrossRef] [PubMed] 4. Schultz, J.L.; Moser, A.D.; Nopoulos, P.C. The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington’s Disease.
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