My research examines inherited metabolic epilepsies with a specific focus on disorders of GABA metabolism. Over the past 15 years, I have studied succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare neurometabolic disorder that can lead to a variety of neurological problems including intellectual deficiency, epilepsy, movement disorders and complex psychiatric symptomology.
My work has involved translational studies, applying principles learned from mouse models to clinical diagnostic and therapeutic trials. In 2009 we published groundbreaking research, showing that GABA (A) and (B) receptors are downregulated in SSADH deficiency, using technology involving flumazenil-PET imaging and later transcranial magnetic stimulation. This reproduced work identified in the animal model using other laboratory techniques, and paved the way for biomarker development and innovative clinical trials that are now in progress.
More broadly, my research encompasses the fields of neurotransmitter disorders and epilepsy. Books that I have authored encapsulate the range of my academic work. Inherited Metabolic Epilepsies, a 2013 publication, has been regarded as a highly innovative approach to this group of disorders. Neuro-Logic, published in 2014, is a primer on localization emanating from my directorship of the medical student preclinical teaching and neurology clerkship in neurology at George Washington School of Medicine and director of the neurology training program at Children’s National Medical Center.
My basic and clinical research has resulted in the following publications that have helped to explain aspects of epilepsy, chiefly shaping our understanding of metabolic epilepsies, including:
Pearl PL, Vezina LG, Saneto RP, McCarter R, Molloy-Wells E, Heffron A, Trzcinski S, McClintock WM, Conry JA, Elling NJ, Goodkin HP, Sotero de Menezes M, Ferri R, Gilles E, Kadom N, Gaillard WD: Cerebral MRI Abnormalities Associated with Vigabatrin Therapy. Epilepsia 2009; 50:184-194.
Pearl PL, Gibson KM, Quezado Z, Dustin I, Taylor J, Trzcinski S, Schreiber J, Forester K, Reeves-Tyer P, Liew C, Shamim S, Herscovitch P, Carson RE, Butman JA, Jakobs C, Theodore WH. Decreased GABA-A Binding on FMZ-PET in Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency. Neurology 2009; 73:423-429.
Pearl PL, Shamim S, Theodore WH, Gibson KM, Forester K, Combs SE, Lewin D, Dustin I, Reeves-Tyer P, Jakobs C, Sato S. Polysomnographic Abnormalities in SSADH Deficiency. Sleep 2009; 32:1645-1648. PMCID: PMC2786049.
Pearl PL, Hyland K, Chiles J, McGavin C, Yuezhu Y, Taylor D: Partial Pyridoxine Responsiveness in PNPO Deficiency. JIMD Rep: 2013;9:139-42. PMCID: PMC3565675.
Yu Y, Shadd WM, Kleifges KA, Myers LA, Pearl PL: Musical Instrument Modifications for Individuals with Neurodevelopmental Disabilities. Music and Medicine 2013 Jul;5(3):145-9. DOI: 10.1177/19438621 13489995.
Pearl PL, McCarter RM, Tsuchida T, Yu Y, Klein P: Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy. Epilepsia 2013 Sep;54(9):e135-137. PMCID: PMC3769484
Pearl PL, Schreiber J, Theodore WH, McCarter R, Barrios ES, Yu YJ, Wiggs E, He J, Gibson KM: Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA. Neurology 2014 Mar 18;82(11):940-944.
Pearl PL, Sable C, Evans S, Knight J, Cunningham P, Lotrecchiano GR, Gropman A, Stuart S, Glass P, Conway A, Ramadan I, Paiva T, Batshaw ML, Packer RJ: International Telemedicine Consultations for Neurodevelopmental Disabilities. Telemed J E Health 2014 Jun;20(6):559-62.
Pearl PL, McConnell E, Fernandez R, Brooks-Kayal A: Survey of the Professors of Child Neurology: Neurology versus Pediatrics Home for Child Neurology. Pediatr Neurol 2014 Sep;51(3):344-347.
Pearl PL, Parviz M, Vogel K, Schreiber J, Theodore WH, Gibson KM. Inherited Disorders of Gamma-aminobutyric Acid Metabolism and Advances in ALDH5A1 Mutation Identification. Dev Med Child Neurol 2014 Dec 29. doi: 10.1111/dmcn.12668.
Lapalme-Remis S, Lewis EC, De Meulemeester C, Chakraborty P, Gibson KM, Torres C, Guberman A, Salomons GS, Jakobs C, Ali-Ridha A, Parviz M, Pearl PL. Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. Neurology. 2015 Sep 8; 85:861-865.
Rodan LH, Gibson KM, Pearl PL. Clinical Use of CSF Neurotransmitters. Pediatr Neurol 2015 Oct;53(4):277-286.
Pearl PL: Inherited Metabolic Epilepsies. New York NY: Demos Publishers; 2013.
Pearl PL and Emsellem HA. Neuro-Logic: A Primer on Localization. New York NY: Demos Medical Publishers; 2014.