Publications

Abstract

  • Outcomes in participants with infantile-onset Niemann-Pick disease type C receiving early and sustained treatment with adrabetadex Elizabeth Berry-Kravis,1* Laurence H. Keller,2 Lixia Jiao,2 Alexander M. Gold,2 Natasa Rajicic,2 David Huang,2 Nicola Longo,3Kristina Julich,4 Jean-Baptiste Le Pichon,5 Randal Richardson,6 Jasmine Knoll,7 Sookyong Koh,8 Young-Min Kim,9 Leigh Maria Ramos-Platt,10 Eugene Kim,10  Ian Rossman,11 Paula P Schleifer,12 Natasha E Shur,13 Joseph L Lasky14 1Rush University, Chicago, IL, USA; 2Beren Therapeutics P.B.C., Thousand Oaks, CA, USA; 3University of California Los Angeles, Los Angeles, CA, USA; 4University of Texas, Austin, TX, USA; 5Children’s Mercy-Kansas City and the University of Missouri-Kansas City, Kansas City, MO, USA; 6Gillette Children’s, St Paul, MN, USA; 7Phoenix Children’s and College of Medicine Phoenix, Phoenix, AZ; 8University of Nebraska Medical Center, Omaha, Nebraska; 9University, Loma Linda, CA, 10Children’s Hospital Lost Angeles, Los Angeles, CA, 11Akron Children’s, Akron, OH, USA; 12Nicklaus Children’s Hospital, Miami, FL, USA; 13Children’s National Hospital, Washington, DC, USA; 14Cure 4 The Kids Foundation, Las Vegas, Nevada, USA;*Presenting author Paragraph summary (lay language): Niemann-Pick disease type C (NPC) is a rare, fatal, genetic disorder in which cells cannot properly transport cholesterol and other lipids, causing these molecules to build up inside many tissues and cause harm, including in important organs like the brain. The disease tends to progress faster and more severely in the youngest affected. Adrabetadex is an investigational therapy being studied ininfantile-onset NPC. Some individuals with NPC received adrabetadex in an expanded access program(EAP). For this presentation, we evaluated 25 children enrolled in the EAP who had symptom onset before 6years of age (infantile onset) and received adrabetadex for at least 5 years. We used the Rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score, which evaluates changes in walking, fine motor skills, speech, and swallowing, to evaluate disease progression in participants who started adrabetadex treatment within 1 year of symptom onset and in participants who started adrabetadex 1 year or more after symptom onset. The results showed that both groups on adrabetadex treatment had much less disease progression than would be expected for young people with infantile-onset NPC. However, participants who started adrabetadex soon after disease onset had improvement or stabilization in NPC symptoms. In contrast, the group of participants who started adrabetadex later, after 1 year of symptom onset, had some disease progression over time, but much less than would be expected without treatment. These early results suggest that early diagnosis and treatment with adrabetadex can slow or reverse disease progression in people withinfantile-onset NPC. Adrabetadex is still under clinical investigation and is not an approved treatment for NPC. Introduction: Niemann-Pick disease type C (NPC) is a lethal, rare, progressive, neurodegenerative genetic disorder caused by impaired cholesterol trafficking. Patients with neurologic symptom onset <6 years of age typically experience progressive neurodegeneration, clinical progression, and premature mortality. Mean (SD) ages of death in patients with neurological onset at <2 years of age and at 2 to <6 years of age have been reported as 5.6 (2.0) years and 13.4 (6.7) years, respectively. Adrabetadex isan investigational treatment designed to transport accumulated cholesterol out of the lysosome and re-establish intracellular cholesterol trafficking in NPC to address the underlying cause of disease. Intrathecal adrabetadex treatment substantially improved overall survival compared with matched external controls and was associated with a significant reduction in the annual rate of neurological disease progression in participants with infantile onset NPC (median age of neurologic onset <6 years of age).This report describes the change in disease progression for participants with infantile-onset NPC (symptom onset <6 years of age) who began adrabetadex treatment within 1 year of neurological symptom onset as well as in those starting treatment after 1 year of onset, with sustained treatment for ≥5 years. Methods: Individuals with NPC were eligible to participate in an intrathecal adrabetadex expanded access program (EAP) thatwas initiated in 2013. In the EAP, dosing of adrabetadex started at 200 mg or 400 mg (depending on age) every 2 weeks with titration up to 1200 mg (initially) or 900 mg (later revision), and dose adjustments were allowed. Outcome measures included the Rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score, which assesses ambulation, fine motor skills, speech, and swallowing. The EAP population was surveyed for participants with disease onset <6 years of age and who had sustained treatment for ≥5 years. Changes in the R4DNPCCSS score from baseline in participants who received treatment with adrabetadex <1 year (prompt treatment group) vs ≥1 year (delayed treatment group) of neurological onset were summarized. Results: Twenty-five participants were included in the analysis: prompt treatment group (n=9) and delayed treatment group (n=16). The age of neurological onset ranged from 0.8 to 5 years and 0 (birth) to 5 years for prompt vs delayed treatment groups, respectively. Time from onset to initiation of adrabetadex ranged from 0.2 to 0.9 years and 1.0 to 12.2 years, respectively. Duration of treatment ranged from approximately 5.3 years to 8.7 years and 5.3 to 11.1 years for the prompt and delayed treatment groups, respectively. Median (min, max) R4DNPCCSS score was lower in the prompt treatment group vs the delayed treatment group: 1.5 (0.0, 4.0) vs 5.0 (2.0, 18.0). At 1, 2, 3, 4, 5, and 6 years post treatment, median (min, max) change from baseline in R4DNPCCSS score in the prompt treatment group was -0.5 (-3.0, 1.0), 0.0 (-4.0, 1.0), -1.0 (-3.0, 0.0), -1.0 (-1.0, 0.0), -1.0 (-1.0, 0.0), and 0.0 (-1.0, 3.0) and in the delayed treatment group was 0.0 (-2.0, 7.0), -0.5 (-3.0, 4.0), 1.0 (-2.0, 6.0), 0.5 (-3.0, 6.0), 1.0 (-3.0, 6.0), and 1.5 (-5.0, 8.0), respectively. Conclusion: In this study, both prompt and delayed treatment groups had substantially improved outcomes based on what would be expected from published natural history study data. As expected, the prompt treatment group had less disease impairment compared with the delayed treatment group prior to starting adrabetadex. The cohort that received prompt treatment showed reduced or similar R4DNPCCSS scores over several years, suggesting improvement or stabilization in NPC symptoms. These initial observational results suggest that early diagnosis and treatment with adrabetadex can slow disease progression in individuals with infantile-onset NPC. (04/2026)
  • Cerebral Palsy Early Detection Initiative Presented at:  Cerebral Palsy Early Detection and Implementation 2020  Presented again at:  National Association of Neonatal Therapists (NANT) annual meeting in 4/2021 The Cerebral Palsy and Movement Disorder Center (CPMDC) at Loma Linda University Children’s Hospital (LLUCH) is a longitudinal, multidisciplinary program that aims to optimize neuroplasticity and comprehensive neurodevelopmental outcomes via early detection, early intervention, and an overall time-sensitive approach.  The Neonatal Intensive Care Unit (NICU) at LLUCH is a level IV, 84 bed facility, the second largest in Southern California.  California Children’s Services (CCS) is a state program that provides diagnostic and treatment services for children under 21 with eligible chronic medical conditions (including cerebral palsy) for families who also qualify based on income level.  The LLUCH High Risk Infant Follow-up Clinic (HRIF) is a neurodevelopmental follow-up clinic for children who qualify per CCS-defined criteria.  The NICU has about 200 newborns per year qualifying for HRIF.  CCS criteria, institutional, institutional clinical practices, evidence-base and research interests were considered. A Modified Define-Measure-Analyze-Improve-Control (DMAIC) Model was used (Figure 1).  Milestones were defined as 1. Integrate the project charter, 2. Identify owners and solutions to barriers, 3. Tasks distributed to work team, 4. Implement, 5-6. 3 and 6 month follow-up. A new clinical service called the 'High Risk Infant / Neonatal Neurology Service' (HRI/NN) was formed (Table 1), and a new NICU-HRIF referral process implemented (Figure 2).  Providers obtained GMA certification and HINE training.  HRIF follow-up schedule was changed to 3-4 months, 8-12 months, and 22-36 months corrected age (plus as needed).   Infants diagnosed with High Risk CP at 3-4 months are referred to CCS medical therapy programs (MTP) and are to be seen at 8 months CA for their second visit.  Infants diagnosed with CP are referred to the multidisciplinary CP clinic (CPC) and to MTP.  This establishes the mechanism for early diagnosis and early intervention in our longitudinal program. (04/2021)
  • A Pathogenic RHOBTB2-variant causes an Angelman-like phenotype. Presented at the American College of Medical Genetics meeting in 2019. (01/2019)

Books and Chapters

  • Chapter 3:  Neurological Examination of Young Children Young-Min Kim Swaiman's Pediatric Neurology:  Principles and Practice, 7th Edition Elsevier, 2025 https://shop.elsevier.com/books/swaimans-pediatric-neurology/ashwal/978-0-443-10944-7 (05/2025)
  • Chapter 4:  Neurological Examination of Infants Young-Min Kim Swaiman's Pediatric Neurology:  Principles and Practice, 7th Edition Elsevier, 2025 https://shop.elsevier.com/books/swaimans-pediatric-neurology/ashwal/978-0-443-10944-7 (05/2025)
  • Chapter 5:  Motor Signs Young-Min Kim, Bhooma Aravamuthan Swaiman's Pediatric Neurology:  Principles and Practice, 7th Edition Elsevier 2025 https://shop.elsevier.com/books/swaimans-pediatric-neurology/ashwal/978-0-443-10944-7 (05/2025)
  • Cerebral Palsy:  Diagnosis Section IV, Chapter 34 Neurodevelopmental Pediatrics: Genetics and Environmental Influences Book chapter on the diagnosis of cerebral palsy. ~150 hours in research and preparing manuscript (02/2023)
  • Cerebral Palsy (1960-present).   Neurodevelopmental Disabilities section of text:  Child Neurology: Its Origins, Founders, Growth and Evolution 2nd Edition.  PUBLISHED 9/2021. History of cerebral palsy from 1960s to present. This book is a history of the field of Pediatric Neurology comprised of historical writings on the development of certain disease concepts, subspecialties, and biosketches.  I wrote the section on the history of cerebral palsy in modern times. Published 9/2021 (09/2021)
  • Contributor to 'Grand Rounds:  Devotional Stories' LLU Press, 2021 (08/2021)
  • Morris, S., Kim, Y.M., Waubant, E., Van Haren, K., Mar, Soe. ‘Acute Flaccid Myelitis.’ Pediatric Demyelinating Disease of the Central Nervous System and Their Mimics:  a case-based clinical guide.  Editors: Lotze, T., Waubant, E. Springer Publications. 2017   (2017)

Scholarly Journals--Published

  • Neurodiversity-Affirming Clinical Care:  Principles and Pearls Talia Shear, MD, Maya Ayoub, MD, Diana Cejas, MD, MPH, Alison Christy, MD, PhD, Yolanda Holler-Managan, MD, Uloma Labrie, MD, Hannah King, MS, and Young-Min Kim, MD Journal of Child Neurology, 2025. Shear T, Ayoub M, Cejas D, et al. Neurodiversity-Affirming Clinical Care: Principles and Pearls. Journal of Child Neurology. 2025;0(0). doi:10.1177/08830738251340268 https://journals.sagepub.com/doi/10.1177/08830738251340268 (05/2025)
  • Kim, YM and Cejas, DM (2023), Empowering differences: Disability in child neurology training. Ann Child Neurol Soc. https://doi.org/10.1002/cns3.20036 First author, letter to editor     (08/2023) (link)
  • Rose Gelineau-Morel, Young-Min Kim, Jennifer A. O'Malley, Jenny L. Wilson, Bhooma R. Aravamuthan. The Role of Child Neurologists in the Management of Motor Disability in Cerebral Palsy: Establishing the Path Forward. Pediatric Neurology, Volume 144, 2023, Pages 33-38, ISSN 0887-8994.  https://doi.org/10.1016/j.pediatrneurol.2023.03.018. (07/2023) (link)
  • Kim, YM, Chin, E.M., Fahey, M., Gelineau-Morel, R., Himmelmann, K., O'Malley, J., Oskoui, M., Shapiro, B., Shevell, M., Wilson, J.L., Wiznitzer, M., and Aravamuthan, B. (2023), SIGnature Libraries: A roadmap for the formation of special interest group libraries. Ann Child Neurol Soc. https://doi.org/10.1002/cns3.20021 Objective “SIGnature Libraries” channel the dynamism of academic society-based special interest groups (SIG) to systematically identify and provide user-oriented access to essential literature for a subspecialty field in a manner that keeps pace with the field's continuing evolution. The libraries include literature beyond clinical trial data to encompass historical context, diagnostic conceptualization, and community organization materials to foster a holistic understanding of how neurologic conditions affect individuals, their community, and their lived experience. Methods Utilizing a modified-Delphi approach, Child Neurology Society's Cerebral Palsy (CP) SIG (n = 75) administered two rounds of literature submissions and ratings. A final review by an 11-member international advisory group determined threshold ratings for resource inclusion and the library's final structure. Results Seventy-nine articles were submitted for the first Delphi round and 22 articles for the second Delphi round. Survey response rates among SIG members were 29/75 for the first round and 24/75 for the second round. The advisory board added additional articles in the final review process in view of the overall project goal. A total of 60 articles were included in the final library, and articles were divided into seven sections and stratified by rating scores. A process for ongoing revisions of the library was determined. The library will be published on the Child Neurology Society website and made publicly accessible. Conclusions The CP SIGnature Library offers learners an unprecedented resource that provides equitable access to latest consensus guidelines, existing seminal datasets, up-to-date review articles, and other patient care tools. A distinctive feature of the library is its intentional large scope and depth, presented in a stratified fashion relative to the consensus-determined importance of each article. Learners can efficiently navigate the library based on individual interests and goals, and the library can be used as core curriculum for CP education. (04/2023)
  • Cerebral palsy in child neurology and neurodevelopmental disabilities training: an unmet need Journal of Child Neurology; https://doi.org/10.1177/08830738211072711 Abstract Background Cerebral palsy (CP) is the most common cause of childhood motor disability. However, there is limited guidance on training of child neurologists and neurodevelopmental disability (NDD) specialists in the care of individuals with CP. We sought to determine training program directors’ impressions of the importance and adequacy of training in the diagnosis and management of CP. Methods In this cross-sectional study, all 82 child neurology and NDD program directors were asked to complete a survey querying program characteristics, aspects of training in CP, importance of CP training, and perceived competence at graduation in CP care. Results There were 35 responses (43% response rate). Nearly all program directors (91%) reported “learning to diagnose CP” as very important and most (71%) felt that “learning to manage CP” was very important. While most program directors reported trainees to be very or extremely competent in CP diagnosis (77%), only 43% of program directors felt that trainees were very or extremely competent in CP management. Time spent with CP faculty was associated with higher reported competence in CP diagnosis (p=0.03) and management (p<0.01). The presence of a CP clinic was associated with higher reported competence in CP management (p=0.03). Conclusions Child neurology and NDD program directors reported that training in CP is important for residents; however, a significant proportion felt that residents were not very well prepared to manage CP. The development of CP curricula and exposure to CP clinics may improve training, translating to better care of individuals with CP. (01/2022)
  • Role of child neurologists and neurodevelopmentalists in the diagnosis of cerebral palsy A survey study Bhooma R. Aravamuthan, Michael Shevell, Young-Min Kim, Jenny L.Wilson, Jennifer A. O'Malley, Toni S. Pearson, Michael C. Kruer, Michael Fahey, Jeff L. Waugh, Barry Russman, Bruce Shapiro, AnnTilton Neurology Oct 2020, 10.1212/WNL.0000000000011036; DOI:10.1212/WNL.0000000000011036 Objective To contextualize the role of child neurologists and neurodevelopmentalists (CN/NDDs) in cerebral palsy (CP) care, we review the changing landscape of CP diagnosis and survey stakeholder CN/NDDs regarding their roles in CP care. Methods The optimal roles of the multiple specialties involved in CP care are currently unclear, particularly regarding CP diagnosis. We developed recommendations regarding the role of CN/NDDs noting: (1) increasing complexity of CP diagnosis given a growing number of genetic etiologies and treatable motor disorders that can be misdiagnosed as CP, and (2) the views of a group of physician stakeholders (CN/NDDs from the Child Neurology Society Cerebral Palsy Special Interest Group). Results CN/NDDs felt that they were optimally suited to diagnose CP. Many (76%) felt CN/NDDs should always be involved in CP diagnosis. However, 42% said their CP patients were typically not diagnosed by CN/NDDs and 18% did not receive referrals to establish the diagnosis of CP at all. CN/NDDs identified areas of their expertise critical for CP diagnosis including knowledge of the neurologic exam across development and early identification of features atypical for CP. This contrasts with their views on CP management, where CN/NDDs felt they could contribute to the medical team, but were necessary primarily when neurologic co-existing conditions were present. Discussion Given its increasing complexity, we recommend early referral for CP diagnosis to a CN/NDD or specialist with comparable expertise. This contrasts with current consensus guidelines which either do not address or do not recommend specific specialist referral for CP diagnosis. (10/2020)
  • Kim, Young-Min et al. A 12-Year-Old Girl With Encephalopathy and Acute Flaccid Paralysis: A Neuropathological Correlation and Cohort Review.  Pediatric Neurology, 2017 Jan; 66:5-11. doi: 10.1016/j.pediatrneurol.2016.08.004. Epub 2016 Sep 8. (01/2017) (link)
  • Ananth AL, Robichaux-Viehoever A, Kim YM, Hanson-Kahn A, Cox R, Enns GM, Strober J, Willing M, Schlaggar BL, Wu YW, Bernstein JA. Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder. Pediatr Neurol. 2016 Jun;59:81-4. doi: 10.1016/j.pediatrneurol.2016.02.018. Epub 2016 Mar 17. (06/2016) (link)
  • Kim, Y.M. ‘late february.’ (2011) Journal of Medical Humanities, 2011; 32:371. (2011)

Online Publications

  • Disability, Advocacy, and Poetry Journal of Child Neurology Podcast https://sageneuroscience.libsyn.com/disability-advocacy-and-poetry  (03/2024)