Pediatric Neurology 2011 Academic Review

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1 Susan Iannaccone, M.D. Professor, Director, Pediatric Nephrology Faculty Pediatric Neurology 2011 Academic Review The Division of Pediatric Neurology is the only academic group in North Central Texas providing consultations and multi-disciplinary care for children with all kinds of neurologic disease. Internationally recognized faculty provide care at Children s Medical Center s Dallas, Legacy and Southlake campuses and at Texas Scottish Rite Hospital for Children (TSRHC). Each member of the faculty provides special expertise in areas of focus including epilepsy and epilepsy surgery, neuromuscular disorders, stroke, demyelinating disease, autism, cerebral palsy and headache. Patients receive a sophisticated and integrated approach to diagnosis including genetic testing, metabolic analysis and interpretation of neuroimaging. Our multidisciplinary clinics include, but are not limited to: Urgent epilepsy Ketogenic diet Myasthenia Childhood stroke Autism Transverse myelitis Neuroncology (directed by Hematology/Oncology) Headache (directed by Pain Management Team) Our group includes 13 full-time faculty based at Children s and two based at TSRHC. In addition, we have one part-time faculty serving in Neuro-oncology and one volunteer faculty serving in a teaching capacity. There are a total of 10 advanced practice providers: two physician assistants and eight nurse practitioners who work alongside our faculty to provide timely and comprehensive care. Susan Arnold, M.D. Michael Dowling, M.D., Ph.D. Patricia Evans, M.D. Sailaja Golla, M.D. Susan Iannaccone, M.D. Professor, Division Director Muna Kahn, M.D. Saadat Kahn, M.D. Fares Kokash, M.D. Rana Said, M.D. Deepa Sirsi, M.D. William Zinser, M.D. In addition to our faculty, the division has: one psychometrician four academic administrative staff one program administrator-clinic one program administrator-epilepsy eleven nursing staff one case manager one social worker one interpreter seven research coordinators one dietitian four clinic techs/ma s two front desk/call center support people Dr. William Zinser retired in December

2 Research Activities Division faculty conduct a variety of neurologic bench/basic research and clinical studies, including clinical trials. Current studies are focused in five areas: metabolic disorders of the nervous system neuromuscular disease clinical trials anti-epileptic drug trials clinical trials in pediatric stroke clinical studies in the autism spectrum Faculty present results of their work at many national and international meetings and published over 30 articles in peerreviewed journals in Dr. Iannaccone is a co-investigator for the NIH Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) which started in October UT Southwestern Neurology is one of 25 sites to participate in this study. NeuroNEXT is designed to increase the efficiency of clinical trials, facilitate patient recruitment and retention, increase the quality of neuroscience clinical trials, and enable public-private partnerships. The network aims to share expertise and infrastructure across diseases, leverage research resources at clinical sites and take advantage of clinical research opportunities as they arise. This clinical research network will provide a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. The network is designed to assure the broadest access to new therapies for patients by carrying out trials coming from partnerships between NINDS and industry, foundations or academia. Clinical Activities The expertise of the faculty is focused on several sub-specialties: comprehensive epilepsy management including seizure surgery; neuromuscular medicine clinics including myasthenia gravis, muscular dystrophy, Charcot Marie Tooth and transitional care for adolescent muscle; cerebrovascular disease; neonatal intensive care follow-up; Zero-2-3 neurodevelopment clinic; rare disorders clinic; and neurodevelopmental disabilities clinics including autism, neurocognitive delay, attention-deficit hyperactivity disorder/learning disabilities (ADHD/LD) and traumatic brain injury. Neurodevelopmental Disabilities Program The Neurodevelopmental Disabilities Program (NDD) concludes its fourth year under the direction of Dr. Patricia Evans at UT Southwestern. The program continues to experience significant growth specifically with regard to clinical opportunities, research, education and community outreach. NDD clinics are multi-disciplinary in structure and are specifically created to serve children with autism, developmental delay, traumatic brain injuries and ADHD/LD issues. The program has expanded to provide full-time NDD services to both the Childrne s Dallas and Legacy campuses. The NDD team serves the North Texas community at large. The team attends special needs children on site at the Dallas-based Autistic Treatment Center on a quarterly basis, and works closely with Dr. Carolyn Garver and her outstanding team of specialists. Drs. Evans and Morris speak throughout the metropolis in various educational settings, including the Dallas ISD, the Dallas Theological Seminary, and other specialty programs regarding children with special needs. Dr. Patricia Evans Epilepsy Program The Epilepsy Program, under the direction of Dr. Susan Arnold, includes a Designated Level 4 Epilepsy Center, the first and only Pediatric Epilepsy program in the Country to be certified by the Joint Commission. The program includes the Children s Epilepsy Monitoring Unit (EMU) that contains eight beds and providing 24/7 coverage for patients in the pediatric intensive care unit (PICU), the neonatal intensive care unit (NICU) and the emergency department. The EMU team includes an attending, support staff, and several third-year medical students on their required neurology rotation plus rotating residents from adult neurology, psychiatry or other specialties. Dr. Susan Arnold 2

3 Neuromuscular Clinic Under the supervision of Dr. Susan Iannaccone the neuromuscular clinic is the only full-time pediatric program in North Texas to be sponsored by the Muscular Dystrophy Association (MDA). The aim of these multidisciplinary clinics are to provide comprehensive health care for the pediatric neuromuscular population. The multidisciplinary approach fosters an environment of all-inclusive health care. Clinic is held four days per week. Stroke Clinic Annual Ketogenic Diet Halloween Party The Pediatric Stroke Clinic, established in 2003, is directed by Dr. Michael Dowling and holds two half-day clinics per week. The patient population consists of children and young adults with arterial ischemic stroke, cerebral venous sinus thrombosis, Sturge-Weber Syndrome, moya-moya or other cerebrovascular disorders. Patients are referred from all parts of Texas, Oklahoma, New Mexico, Arkansas, Louisiana and the United Kingdom. Dr. Michael Dowling The Multidisciplinary Stroke Clinic sees patients twice monthly for half days. Dr. Dowling established this clinic in October 2007 and meets twice monthly with attendings from Pediatric Hematology, Physical Medicine and Rehabilitation and Neuropsychology, as well as research nurses for coordinated patient visits (approximately four patients per clinic). This serves as a unique clinical and teaching program, with involvement of medical students, Pediatric Psychiatry fellows, Pediatric Neurology fellows, Adult Neurology residents, and Physical Medicine and Rehabilitation fellows. The Acute Stroke Team is on call 24 / 7 / 365 for any stroke or suspected stroke in a Children s Dallas or Legacy campus patient. Dr. Dowling provides emergent telephone consultation with in-person evaluation and treatment in the emergency setting and follows the patients clinically alongside the neurology inpatient service. Neurology Patient Visits Epilepsy 4,574 General Neurology 683 Headache 935 Neuromuscular 1,010 Neurodevelopment 832 Rare Disorders 106 Research 162 Residents 519 Stroke/Sickle Cell 260 Demyelinating 268 Faculty 6,871 APPs 2,532 Total 9,403 3

4 Education and Training Our three-year training program for pediatric neurology is the only one in north Texas and is highly competitive. Our residency for neurodevelopmental disabilities is one of only seven in the country. We graduate three pediatric neurologists each year and offer subspecialty fellowships in epilepsy, neurophysiology, demyelinating disease, and neuromuscular medicine for our graduates as well as candidates from other programs. Dr. Rana Said, Program Director for the pediatric neurology residency and clerkship, leads the teaching program that educates residents and medical students for inpatient and outpatient rotations, with the assistance of Program Coordinator, Kellie Shaw. The program includes: two adult neurology residents for three four-week blocks each, seven UT Southwestern Internal Medicine residents for two months each, one to three adult and pediatric neurophysiology/epilepsy fellows, and one to three neuromuscular medicine fellows for one year each. More than 200 medical student neurology clerkship participants rotate for two-week intervals on either inpatient or outpatient rotations each year. The faculty participates in up to eight neurology teaching conferences per week as well as a series of pediatric teaching conferences on neurologic topics. The Carrell-Krusen Neuromuscular Symposium is held annually in February. Dr. Susan Iannaccone is the course director for this symposium designed for muscular dystrophy clinic directors, case managers, nurses and members of interdisciplinary teams. The focus is on protocols for treatment and management of both common and unusual neuromuscular disorders, identifying characteristic findings on muscle biopsies and EMG studies, and describing recent advances in basic and clinical research in neuromuscular disorders. Presentations Michael M. Dowling, M.D., Ph.D., M.S.C.S. Ichord RN, Bastian R, Abraham L, Askalan R, Benedict S, Bernard T, Beslow L, deveber G, Dowling M, Friedman M, Fullerton H, Jordan L, Kirton A, Amlie-Lefond C, Licht D, Lo W, McClure C, Pavlakis S, Smith SE, Tan M, Jawad AF. Inter-observer Reliability of the Pediatric NIH Stroke Scale (PedNIHSS) in a Multicenter Study, International Stroke Conference, Los Angeles, CA, February 2011 PFO and Stroke in SCD, Hematology Clinical Research Seminar, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, OH, June 2011 Sickle Cell in Focus, Stroke and Cerebrovascular Complications of Sickle Cell Disease, Kings College, London, UK, June 2011 Stroke in Children, Texas Pediatric Society Annual Meeting Plenary Session, Sugarland, TX, September

5 Dowling MM, Hynan L, Lo W, Licht D, McClure C, Yager J, Dlamini N, Kirkham F, deveber G, Pavlakis S. International Pediatric Stroke Study: Stroke Associated with Cardiac Disorders, World Congress of Neurology, Marrakesh, Morocco, November 2011 Quinn CT, Hoof PD, Dowling MM. Cerebral Tissue Desaturation in Children with Sickle Cell Disease, American Hematology Society Annual Meeting, San Diego, CA, December 2011 Patricia Evans, M.D. Reel Docs, Film Series, Dr. Temple Grandin, Documentary on Autism, June 2011 Autistic Spectrum Disorder, University of Texas Permian Basin, July 2011 Susan T. Iannaccone, M.D. An Overview - Recent Advances in SMA and Other Pediatric Neuromuscular Diseases, Texas Scottish Rite Hospital for Children, Dallas, February 2011 Standard of Care for Duchenne Muscular Dystrophy - Recent Advances in SMA and Other Pediatric Neuromuscular Diseases, Northwestern University Medical Center, Chicago, IL, May 2011 Juan M. Pascual, M.D., Ph.D. 3 rd Symposium on Glucose Transporter Deficiency, New Orleans, LA, July 2011 Rana R. Said, M.D. Neurological Disorders: Seizures, Headaches, Brain Tumors, Neurodegenerative and Neuromuscular Disorders, American Academy of Child & Adolescent Psychiatry (AACAP), Honolulu, Hawaii, March 2011 Epilepsy Management: In the Office and ER, Children s Medical Center at Legacy, November 2011 Early Surgical Treatment of Infants with Catastrophic Epilepsy Symptomatic to Cortical Dysplasias, American Academy of Neurology Annual Meeting, Honolulu, Hawaii, April 2011 Awards and Honors Susan Arnold, M.D. Top US Doctors, U.S. News & World Report Michael Dowling, M.D., Ph.D., M.S.C.S. Susan Iannaccone, M.D. Texas Super Doctors, Texas Monthly Top US Doctors, U.S. News & World Report Rana Said, M.D. Child Neurology Residents Program Director Appreciation Award Publications Articles 1. Castro D, Iannaccone ST, Gilbreath H, et al. Juvenile myasthenia gravis: a twenty year experience (33rd Annual Carrell-Krusen Neuromuscular Symposium, Texas Scottish Rite Hospital for Children, Dallas, Texas, February 17-18, 2011). J Clin Neuromuscular Disease 2011;12:17: Choi C, Ganji SK, DeBerardinis RJ, Dimitrov IE, Pascual JM, et al. Measurement of glycine in the human brain in vivo by 1H-MRS at 3 T: application in brain tumors. Magn Reson Med;66: Derisavifard S, Castro C, Guleserian K, Iannaccone ST, Andersen M, Greene M. Juvenile myasthenia gravis: a twentyyear experience. Neurology 2011;76:A94 (Suppl 4). 4. Gilbreath H, Iannaccone ST, Bonnemann C. Variable phenotypes in Ullrich congenital muscular dystrophy (33rd Annual Carrell-Krusen Neuromuscular Symposium, Texas Scottish Rite Hospital for Children, Dallas, Texas, February 17-18, 2011). J Clin Neuromuscular Disease 2011;12:7: Ichord RN, Bastian R, Abraham L, Askalan R, Benedict S, Bernard TJ, Beslow L, Deveber G, Dowling M, et al. Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke;42: Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, et al. Natural history of MELAS associated with mitochondrial DNA m.3243a>g genotype. Neurology;77: Marin-Valencia I, Good LB, Ma Q, Jeffrey FM, Malloy CR, Pascual JM. High-resolution detection of (1)(3)C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy. J Neurosci Methods;203: Montgomery M, Joyce C, Iannaccone ST, et al. Utilizing a national continuing medical education (CME) series to highlight emerging therapeutic opportunities in spinal muscular atrophy (SMA). Neurology 2011;76:A94 (Suppl 4). 5

6 9. Pascual JM. Animal models of the human mind: Is there anything like being autistic? Neurosci Lett;505: Pascual JM. Synaptic transporters are deceived if they think themselves free. Neurosci Lett;487: Perez-Duenas B, Ormazabal A, Toma C, Torrico B, Cormand B, Serrano M, Sierra C, De Grandis E, Marfa MP, Garcia-Cazorla A, Campistol J, Pascual JM, Artuch R. Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol;68: Rogers ZR, Wang WC, Luo Z, Iyer RV, Shalaby-Rana E, Dertinger SD, Shulkin BL, Miller JH, Files B, Lane PA, Thompson BW, Miller ST, Ware RE, BABY HUG Investigators (including Dowling M). Biomarkers of splenic function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. Blood;117: Scharner J, Brown CA, Bower M, Iannaccone ST, et al. Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations. Hum Mutat;32: Sirsi D. Is intranasal midazolam better than rectal diazepam for home management of acute seizures? Arch Neurol;68: Tang W, Gilbreath H, Burns D, Iannaccone ST. Heat or exercise-induced rhabdomyolysis in ryanodine receptor channelopathy (33rd Annual Carrell-Krusen Neuromuscular Symposium, Texas Scottish Rite Hospital for Children, Dallas, Texas, February 17-18, 2011). J Clin Neuromuscular Disease 2011;12:13: Wadman RI, Bosboom WM, van den Berg LH, Wokke JH, Iannaccone ST, Vrancken AF. Drug treatment for spinal muscular atrophy types II and III. Cochrane Database Syst Rev:CD Wadman RI, Bosboom WM, van den Berg LH, Wokke JH, Iannaccone ST, Vrancken AF. Drug treatment for spinal muscular atrophy type I. Cochrane Database Syst Rev:CD Waugh J, Plumb P, Rollins N, Dowling MM. Prolonged direct catheter thrombolysis of cerebral venous sinus thrombosis in children: a case series. J Child Neurol;27: Zimmerman A, Clemens PR, Tesi-Rocha C, Connolly A, Iannaccone ST, et al. Liquid formulation of pentoxifylline is a poorly tolerated treatment for duchenne dystrophy. Muscle Nerve;44: Book Sections 1. Evans P. End-of-life-care for the neurologically impaired child. In: William, McGuire, Rizzo, eds. Practical Ethics in Clinical Neurology. Philadelphia, PA: American Academy of Neurology, LIppincott, Wilkins and Williams; Evans P. Informed assent and refusal for children and adolescents. In: William, McGuire, Rizzo, eds. Practical Ethics in Clinical Neurology. Philadelphia, PA: American Academy of Neurology, LIppincott, Wilkins and Williams; Evans P. Why, O God? A Biblical theology of suffering and disability. In: Water L, ed. Practicing Inclusivity for Children with Special Needs. Wheaton, IL: Good News and Crossways Publishers; Pascual JM. Disorders of muscle excitability. In: Brady ST, Siegel GJ, Albers RW, Price DL, eds. Basic Neurochemistry. 8th ed: Elsevier; Pascual JM, DiMauro S. Disorders of the Krebs cycle and of pyruvate metabolism and transport. In: Rudolph CD, Rudolph AM, Lister G, First LR, Gershon AA, eds. Rudolph s Pediatrics, 22nd edition. New York, NY: McGraw Hill; Grants Sponsored Clinical Trials Susan Arnold, M.D. Safety and Effectiveness of Open-Label Clobazam in Subjects with Lennox-Gastuat Syndrome Ovation Pharmaceuticals, OV-1004 Random, Double-Blind, Placebo-Controled, Parallel-Group Study with Open-Label Ext. Phase to Evaluate Effect of Perampanel (E2007) on Cognition, Growth, Safety, Tolerability and Pharmocokinetics when Administered as Adjunctive Therapy in Adolescents (12 to <18 yrs) with Inadequately Controled Partial-Onset Seizures Eisai Medical Research, Inc., E2007-G Open-Label Ext. Phase of Double-Blind Placebo-Controlled Study of E2007 (perampanel) Given as Adjunctive Therapy in Subjects with Refractory Partial Seizures Eisai Medical Research, Inc., E2007-G

7 Double Blind Placebo Controlled Dose-Escalation Study of E2007 (perampanel) Given as Adjunctive Therapy in Subjects with Refractory Partial Seizures Eisai Medical Research, Inc., E2007-G Susan Iannaccone, M.D. Open-Label Safety Study for Previously Treated Ataluren (PTC124) Patients with Nonsense Mutation Dystrophinopathy PTC Therapeutics, Inc., PTC124-GD-016-DMD Phase 2b Study of PTC124 in Subjects with Nonsense-Mutation-Mediated Duchenne and Becker Muscular Dystrophy PTC Therapeutics, Inc., PTC124-GD-007(e)-DMD 7

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