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Maria Luisa Escolar

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This sandbox is in the article namespace. Either move this page into your userspace, or remove the {{User sandbox}} template. Maria Luisa Escolar is a pediatrician, clinical professor, and researcher who specializes in pediatric neurodevelopmental disabilities. She is Founder and Director of the Program for the Study of Neurodevelopment in Rare Disorders at Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center.[1] Escolar is nationally and internationally known for her research and clinical care of children with leukodystrophies, lysosomal storage diseases, and other inherited metabolic diseases.[2]

Biography

Maria Luisa Escolar earned a medical degree at Escuela Colombiana de Medicina in Bogotá, Colombia in 1986; Master of Science in Human Nutrition at Columbia University College of Physicians and Surgeons, New York, NY in 1988; and continued her training in Child Development and Behavioral Pediatrics at New York Hospital–Cornell Medical Center.[3][4]

In 2000 Escolar established the Early Childhood Clinic at the Clinical Center for the Study of Development and Learning at the University of North Carolina at Chapel Hill to provide comprehensive care for children affected by Krabbe disease and other lysosomal storage disorders.[3] This program became the Neurodevelopmental Function in Rare Disorders and gradually expanded to include other rare neurodegenerative disorders.[3] In 2011, the program moved to the Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center and was renamed the Program for the Study of Neurodevelopment in Rare Disorders.[1]

Escolar’s work as a pediatrician specializing in rare neurodevelopmental diseases has become well known through word of mouth and media.[5][6][7][8][9][10][11][12][13][14] Escolar has developed multidisciplinary approaches to diagnose these diseases and assess disease progression and treatment outcomes.[15] She has contributed to articles on the management of mucopolysaccharidosis type II (Hunter syndrome)[16] and assessment of neurodevelopment in lysosomal storage diseases and related disorders using standardized and validated tools.[17]

NDRD clinic

As a clinical associate in pediatrics at Duke University Medical Center, Escolar saw her first patient with Krabbe disease while evaluating outcomes of umbilical cord blood transplantation in children with lysosomal storage disorders.[3][18] Successful management of disease symptoms in this patient led to referrals of other children with lysosomal storage disorders and to the awareness that few physicians had sufficient knowledge to care for these children.[18] To provide more comprehensive care at earlier disease stages and collect data for natural history studies, she established the Early Childhood Clinic at the Clinical Center for Development and Learning at the Carolina Institute for Developmental Disabilities, University of North Carolina–Chapel Hill, which evolved into the Program for Neurodevelopmental Function in Rare Disorders (NFRD).[3]

In 2011, Escolar joined the Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, and the program was renamed the Program for the Study of Neurodevelopment in Rare Disorders (NDRD).[15] The NDRD provides clinical services, conducts research, and trains clinicians, researchers, and students.[19] Escolar has particular expertise in Krabbe disease but also sees patients with other neurodegenerative diseases including metachromatic leukodystrophy, adrenoleukodystrophy, and mucopolysaccharidosis disorders.[20]

Clinic visits typically include assessments by a neurodevelopmental pediatrician, neurologist, ophthalmologist, audiologist, physical therapist, and nurse practitioner, who provide recommendations for symptom management, schooling, therapies, and palliative care.[1] As of May 2015, the program was following more than 700 patients from 40 US states and 20 countries.[19] Escolar also consults with families of affected children who are unable to travel to the clinic and with their doctors through the NDRD Virtual Medical Home.[19][21]


Rare disease research

Escolar’s research focuses on describing the natural history of rare neurodegenerative conditions and developing qualitative and quantitative methods to assess treatment outcomes and monitor disease progression. She has also contributed to the characterization of neurophysiologic abnormalities in mucopolysaccharidosis type III (Sanfilippo syndrome)[22] and development of a potential biochemical biomarker that may aid in newborn screening for Krabbe disease.[23] In 2010 Escolar created the Krabbe Translational Research Network, a consortium of clinicians and researchers who are working together on specific projects to improve treatments for Krabbe disease[24][25]

Treatment outcomes

While assessing treatment outcomes of children undergoing umbilical cord blood transplantation at Duke University Hospital, Escolar hypothesized that treatment of children with Krabbe disease would be more effective if performed earlier in the disease process.[3] To test that hypothesis, Escolar and colleagues compared treatment outcomes of patients with infantile Krabbe disease identified through family history who were symptomatic or asymptomatic at the time of treatment. In the short term, umbilical cord blood transplantation improved neurodevelopmental function and survival.[26] A follow-up study reported that most of the children treated while still asymptomatic had normal cognitive function, vision, and hearing 10 years after transplantation but experienced varying degrees of motor disability, growth failure, and speech difficulties.[27]

Escolar has also studied treatment outcomes in other neurodegenerative diseases and has recommended specific standardized assessment instruments to evaluate outcomes in children with Hurler syndrome.[28] Escolar and colleagues report that early treatment with umbilical cord blood transplantation can improve somatic impairment, cognitive function, and motor skills in children with mucopolysaccharidosis type I (Hurler syndrome);[29][30][31] adaptive behavior and cognitive, language, and motor skills in boys with adrenoleukodystrophy;[32] and hearing, neurodevelopment, and skeletal abnormalities in children with alpha-mannosidosis.[33]

Natural history studies

After beginning to provide clinical services for children with rare neurodegenerative diseases, Escolar realized the need for natural history studies. Systematic collection of clinical data has resulted in a database of information on more 700 patients.[1][3][19] These studies are used to better understand disease progression, distinguish among disease subtypes, improve diagnostic tests, define endpoints for clinical trials, and evaluate response to treatment.[19][34][35][36] She has published or contributed to natural history studies on Sanfilippo syndrome type A [37] and studies evaluating transplantation outcomes for patients with Hurler syndrome[38][39] and metachromatic leukodystrophy.[40]

Clinical tools for detecting neurodegenerative disease

Escolar has worked with other clinicians to identify tools that could help decrease the time to diagnosis and identify patients with early-onset forms of these diseases that require urgent treatment decisions. With Dr. Stephanie Wolfe, a child neurology specialist at the University of North Carolina, Escolar developed the Protocol for the Assessment of Neurodevelopmental Function in Early Infancy (PANDI) to detect developmental delays at an early age, predict future neurodevelopment, and give parents the information they need to provide their children with early interventions.[41][42] With Dr. Joanne Kurtzberg, a pediatric transplant specialist at Duke University Hospital, Escolar and the NFRD staff developed a staging system to help physicians determine whether a patient with Krabbe disease was a good candidate for transplantation. The patient’s pretransplant stage, based on clinical signs and symptoms, is used to predict neurodevelopmental outcomes after treatment.[43]

To assess neurodevelopmental changes in children with lysosomal storage diseases and related disorders, Escolar and the NDRD staff developed a multidisciplinary approach using a combination of standardized and validated tests.[44] These tests can be used for the longitudinal tracking of development (speech/language, cognition, and fine and gross motor development, and adaptive behavior) and take into account limitations caused by neurological, sensory and somatic problems. To identify which patients with mucopolysaccharidosis type II (Hunter syndrome) have the severe neurodegenerative form of the disease, Escolar’s group developed a severity score index based on clinical markers of neurologic disease as a screening tool.[45]

Neuroimaging tools for diagnosis and evaluation of disease progression

Because clinical evaluations of children at risk for Krabbe disease are not easily reproducible, Escolar has collaborated with neuroradiologists to develop better tools to diagnose this and other neurodegenerative diseases and to evaluate disease progression, effects of treatment on different brain regions, and the development and timing of myelination.[46][3][47][48][49][50][51][52][53][54][55]

Escolar and collaborators have reported that diffusion tensor imaging tractography with white matter volumetric analysis can detect white matter changes in the early stages of infantile Krabbe disease before symptoms are apparent.[56] A subsequent study showed that reductions in fractional anisotropy in the corticospinal tract can predict response to treatment and long-term neurodevelopment (longitudinal changes in cognitive function, motor skills, and adaptive behavior).[57]

In 2015, Escolar and colleagues developed a simple scoring system of midbrain morphology, as determined by magnetic resonance imaging, to assess disease severity in infantile Krabbe disease. Their research showed that flat or concave morphology of the midbrain correlates with poorer cognitive and gross motor function.[58]

NDRD training program

Because few physicians specialize in rare neurodevelopmental disorders, Escolar has developed a training program for students, physicians, and other specialists including those in the fields of psychology, speech/language pathology, audiology, physical therapy, occupational therapy, nutrition, education, social work, biostatistics, and nursing.[59][60] In addition, she serves as a consultant to establish similar clinics in other countries.[61][62]

References

  1. ^ a b c d "Program for the Study of Neurodevelopment in Rare Disorders (NDRD)". Chp.edu. Retrieved 2015-07-19.
  2. ^ "Physicians and Staff". Chp.edu. 2014-08-20. Retrieved 2015-07-19.
  3. ^ a b c d e f g h http://caterinamarcusfoundation.org/resources/UNC%20Medical%20Bulletin%20Fall%2008.pdf
  4. ^ "Escolar, Maria Luisa, MD, MS". Chp.edu. 2013-05-16. Retrieved 2015-07-19.
  5. ^ http://www.post-gazette.com/news/health/2013/10/ prog05/Pittsburgh-s-Children-s-Hospital-doctor-dedicated-to-treating-those-with-rare-disorders/stories/201310050062
  6. ^ North, Campbell (2014-12-04). "Patient advocacy crucial in fighting rare diseases | Pittsburgh Post-Gazette". Post-gazette.com. Retrieved 2015-07-19.
  7. ^ "Fund-raiser set for tot with rare genetic disorder". Toledo Blade. Retrieved 2015-07-19.
  8. ^ "Rare, fatal disease afflicts Kiski 4-year-old". TribLIVE. Retrieved 2015-07-19.
  9. ^ By David Chang. "Local Girl With Rare Disease Inspires Nationwide Support | NBC 10 Philadelphia". Nbcphiladelphia.com. Retrieved 2015-07-19.
  10. ^ "Krabbe Disease awareness". NJ.com. 2010-09-26. Retrieved 2015-07-19.
  11. ^ Barbara Miller/PennLive.com (2013-09-02). "Grandparents of girl with rare disease urge tests in hopes other children may be spared". PennLive.com. Retrieved 2015-07-19.
  12. ^ "‘Worst nightmare'". SoMdNews.com. Retrieved 2015-07-19. {{cite web}}: C1 control character in |title= at position 1 (help)
  13. ^ "Parents say $1 test could have changed son's life - CBS News 8 - San Diego, CA News Station - KFMB Channel 8". Cbs8.com. Retrieved 2015-07-19.
  14. ^ http://www.huntershope.org/site/DocServer/Stutzman_Interview_with_Jewish_News_of_Greater_Phoenix.pdf?docID=12742
  15. ^ a b "Insights Fall 2011". Insights.pipitonegroup.com. Retrieved 2015-07-19.
  16. ^ Muenzer J, Beck M, Eng CM, Escolar ML, Giugliani R, Guffon NH, Harmatz P, Kamin W, Kampmann C, Koseoglu ST, Link B, Martin RA, Molter DW, Muñoz Rojas MV, Ogilvie JW, Parini R, Ramaswami U, Scarpa M, Schwartz IV, Wood RE, Wraith E. Multidisciplinary management of Hunter’s syndrome. Pediatr. 2009 Dec;124(6):e1228-e39. DOI: 10.1542/peds.2008-0999
  17. ^ Martin H, Poe MD, Reinhartsen D, Pretzel RE, Roush J, Rosenberg A, Dusing SC, Escolar ML. Methods for assessing lysosomal storage and related disorders: a multidisciplinary perspective. Acta Paediatr Suppl. 2007 Apr;97(457):69-75. DOI: 10.1111/j.1651-2227.2008.00651.x.
  18. ^ a b "Maria Luisa Escolar, MD, MS". YouTube. 2014-10-30. Retrieved 2015-07-19.
  19. ^ a b c d e "Neurodevelopment in Rare Disorders". YouTube. 2015-07-14. Retrieved 2015-07-19.
  20. ^ "Using Cord Blood to Treat Neurodegenerative Diseases". YouTube. 2013-04-24. Retrieved 2015-07-19.
  21. ^ "Neurodevelopment in Rare Disorders (NDRD) Home". Ndrdvirtualmed.com. Retrieved 2015-07-19.
  22. ^ Husain AM, Escolar ML, Kurtzberg J. Neurophysiologic assessment of mucopolysaccharidosis III. Clin Neurophysiol. 2006 Sep;117(9):2059-063. DOI: http://dx.doi.org/10.1016/j.clinph.2006.05.031.
  23. ^ Turgeon CT, Orsini JJ, Sanders KA, Magera MJ, Langan TJ, Escolar ML, Duffner P, Oglesbee D, Gavrilov D, Tortorelli S, Rinaldo P, Raymond K, Matern D, Measurement of psychosine in dried blood spots - a possible improvement to newborn screening programs for Krabbe disease. J Inherit Metab Dis. 2015 Mar 12. DOI: 10.1007/s10545-015-9822-z
  24. ^ "Neurodevelopment in Rare Disorders (NDRD): Krabbe Translational Research Network (KTRN)". Ndrdvirtualmed.com. Retrieved 2015-07-19.
  25. ^ "Krabbe Disease KTRN". Tloaf.org. Retrieved 2015-07-19.
  26. ^ Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. DOI: 10.1056/NEJMoa042604
  27. ^ Escolar ML, Yelin K, Poe MD. Neurodevelopmental outcome of children with infantile Krabbe disease treated with umbilical cord blood transplantation: 10 years of follow up. Lysosomal Storage Dis. 2006;6(3):71-9.
  28. ^ Dusing SC, Rosenberg A, Hiemenz JR, Piner S, Escolar M. Gross and fine motor skills of children with Hurler syndrome (MPS-IH) post umbilical cord blood transplantation: a case series report. Pediatr Phys Ther. 2005 Winter;17(4):264-7. DOI: 10.1097/01.pep.0000186510.37581.19.
  29. ^ Poe MD, Chagnon SL, Escolar ML. Early treatment is associated with improved cognition in Hurler syndrome. Ann Neurol. 2014 Nov;76(5):747-53. DOI: 10.1002/ana.24246.
  30. ^ Coletti HY, Aldenhoven M, Yelin K, Poe MD, Kurtzberg J, Escolar ML. Long-term functional outcomes of children with hurler syndrome treated with unrelated umbilical cord blood transplantation. JIMD Rep. 2015;20:77-86. DOI: 10.1007/8904_2014_395.
  31. ^ Dusing SC, Thorpe DE, Mercer VS, Rosenberg AE, Poe MD, Escolar ML. Temporal and spatial gait characteristics of children with Hurler syndrome after umbilical cord blood transplantation. Phys Ther. 2007 Aug;87(8)978-85. DOI: 10.2522/ptj.20060196.
  32. ^ Beam D, Poe M.D, Provenzale JM, Szabolcs P, Martin PL, Prasad V, Parikh S, Driscoll T, Kurtzberg J, Escolar ML. Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy. Biol Blood Marrow Transplant. 2007 Jun;13(6):665-74. DOI: http://dx.doi.org/10.1016/j.bbmt.2007.01.082
  33. ^ Mynarek M, Tolar J, Albert MH, Escolar ML, Boelens JJ, Cowan MJ, Finnegan N, Glomstein A, Jacobsohn DA, Kühl H, Kurtzberg J, Malm D, Orchard PJ, Klein C, Lücke T, Sykora K-W. Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients. Bone Marrow Transplant. 2012 Mar;47(3):352-9. DOI: 10.1038/bmt.2011.99.
  34. ^ Buhrman D, Thakkar K, Poe M, Escolar ML. Natural history of Sanfilippo syndrome type A. J Inherit Metab Dis. 2014 May;37(3):431-7. DOI: 10.1007/s10545-013-9661-8.
  35. ^ Holt JB, Poe MD, Escolar ML. Natural progression of neurological disease in mucopolysaccharidosis type II. Pediatrics. 2011 May;127(5):e1258-65. DOI: 10.1542/peds.2010-1274.
  36. ^ http://ndrdvirtualmed.com/research.shtml
  37. ^ Buhrman D, Thakkar K, Poe M, Escolar ML. Natural history of Sanfilippo syndrome type A. J Inherit Metab Dis. 2014;37(3):431-7. DOI: 10.1007/s10545-013-9661-8.
  38. ^ Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit, W, Kurtzberg J. Cord-blood transplants from unrelated donors in patients with hurler's syndrome. N Engl J Med. 2004 May;350(19):1960-9. DOI: 10.1056/NEJMoa032613.
  39. ^ Boelens JJ, Aldenhoven M, Purtill D, Ruggeri A, Defor T, Wynn R, Wraith E, Cavazzana-Calvo M, Rovelli A, Fischer A, Tolar J, Prasad VK, Escolar M, Gluckman E, O'Meara A, Orchard PJ, Veys P, Eapen M, Kurtzberg J, Rocha V; Eurocord; Inborn Errors Working Party of European Blood and Marrow Transplant group; Duke University Blood and Marrow Transplantation Program; Centre for International Blood and Marrow Research. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood. 2013 May 9;121(19):3981-7. DOI: 10.1182/blood-2012-09-455238.
  40. ^ Martin HR, Poe MD, Provenzale JM, Kurtzberg J, Mendizabal A, Escolar ML. Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy. Biol Blood Marrow Transplant. 2013 Apr;19(4): 616-24. DOI: 10.1016/j.bbmt.2013.01.010.
  41. ^ "40th Annual John B. Graham Research Society Abstracts — Howard Holderness Distinguished Medical Scholars Program". Med.unc.edu. Retrieved 2015-07-19.
  42. ^ "Neurodevelopment in Rare Disorders (NDRD): Protocol for the Assessment of Neurodevelopmental Function in Early Infancy (PANDI)". Ndrdvirtualmed.com. Retrieved 2015-07-19.
  43. ^ Escolar ML, Poe MD, Martin HR, Kurtzberg J. A staging system for infantile Krabbe disease to predict outcome after unrelated umbilical cord blood transplantation. Pediatrics. 2006 Sep;118(3):e879-89. DOI: doi: 10.1542/peds.2006-0747
  44. ^ Martin HR, Poe MD, Reinhartsen D, Pretzel RE, Roush J, Rosenberg A, Dusing SC, Escolar ML. Methods for assessing neurodevelopment in lysosomal storage diseases and related disorders: a multidisciplinary perspective. Acta Paediatr Suppl. 2008 Apr;97(457):69-75. DOI: 10.1111/j.1651-2227.2008.00651.x.
  45. ^ Holt J, Poe MD, Escolar ML. Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II. J Pediatr. 2011 Aug;159(2):320-6. DOI: 10.1016/j.jpeds.2011.03.019.
  46. ^ http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/nominatecondition/reviews/krabbedisease.pdf
  47. ^ Sharma A, Fletcher PT, Gilmore JH, Escolar ML, Gupta A, Styner M, Gerig G. Parametric regression scheme for distributions: analysis of DTI fiber tract diffusion changes in early brain development. Proc IEEE Int Symp Biomed Imaging. 2014:559-562. DOI: DOI: 10.1109/ISBI.2014.6867932
  48. ^ Gupta A, Toews M, Janardhana R, Rathi Y, Gilmore J, Escolar M, Styner M. Fiber feature map based landmark initialization for highly deformable DTI registration. Proc SPIE Int Soc Opt Eng. 2013 Mar 13;8669. DOI: 10.1117/12.2006977.
  49. ^ Sharma A, Fletcher PT, Gilmore JH, Escolar ML, Gupta A, Styner M, Gerig G. Spatiotemporal modeling of discrete-time distribution-valued data applied to DTI tract evolution in infant neurodevelopment. Proc IEEE Int Symp Biomed Imaging. 2013;2013:684-687. DOI: 10.1109/ISBI.2013.6556567
  50. ^ Farzinfar M, Oguz I, Smith RG, Verde AR, Dietrich C, Gupta A, Escolar ML, Piven J, Pujol S, Vachet C, Gouttard S, Gerig G, Dager S, McKinstry RC, Paterson S, Evans AC; IBIS network, Styner MA. Diffusion imaging quality control via entropy of principal direction distribution. Neuroimage. 2013;82:1-12. DOI: 10.1016/j.neuroimage.2013.05.022.
  51. ^ Wang Y, Gupta A, Liu Z, Zhang H, Escolar ML, Gilmore JH, Gouttard S, Fillard P, Maltbie E, Gerig G, Styner M. DTI registration in atlas based fiber analysis of infantile Krabbe disease. Neuroimage. 2011 Apr;55 (4):1577-86. DOI: 10.1016/j.neuroimage.2011.01.038.
  52. ^ Fan Z, Styner M, Muenzer J, Poe MD, Escolar, ML. Correlation of automated volumetric analysis of brain MR imaging with cognitive impairment in a natural history study of mucopolysaccharidosis II. AJNR Am J Neuroradiol. 2010 Aug;31(7):1319-23. DOI: 10.3174/ajnr.A2032.
  53. ^ Provenzale JM, Peddi S, Kurtzberg J, Poe MD, Mukundan S, Escolar M. Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's disease. AJR Am J Roentgenol. 2009 Jan;192(1):59-65. DOI: 10.2214/AJR.07.3885.
  54. ^ Provenzale JM, Escolar M, Kurtzberg J. Quantitative analysis of diffusion tensor imaging data in serial assessment of Krabbe disease. Ann N Y Acad Sci. 2005 Dec;1064:220-9. DOI: 10.1196/annals.1340.040
  55. ^ McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM. Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology. 2005 Jul;236(1):221-30. DOI: http://dx.doi.org/10.1148/radiol.2353040716
  56. ^ Escolar ML, Poe MD, Smith JK, Gilmore JH, Kurtzberg J, Lin W, Styner M. Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease. AJNR Am J Neuroradiol. 2009 May;30(5):1017-21. AJNR Am J Neuroradiol. 2009 May;30(5):1017-21. DOI: 10.3174/ajnr.A1476
  57. ^ Gupta A, Poe MD, Styner MA, Panigrahy A, Escolar ML. Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease. Neuroimage Clin. 2014 Sep 26;7:792-8. DOI: 10.1016/j.nicl.2014.09.014.
  58. ^ Zuccoli G, Narayanan S, Panigrahy A, Poe MD, Escolar ML. Midbrain morphology reflects extent of brain damage in Krabbe disease. Neuroradiology. 2015 Apr 10. DOI: 10.1007/s00234-015-1523-7.
  59. ^ "NDRD Training Program". Chp.edu. 2013-07-25. Retrieved 2015-07-19.
  60. ^ "Caterina Marcus Foundation". Caterina Marcus Foundation. Retrieved 2015-07-19.
  61. ^ "Brain Care Institute: Dr. Maria Escolar". YouTube. 2012-08-13. Retrieved 2015-07-19.
  62. ^ "International Collaborations". Chp.edu. 2014-10-28. Retrieved 2015-07-19.
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