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Maria Luisa Escolar

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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

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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

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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

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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

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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

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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

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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. Michele Poe, 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

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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.[3][46][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

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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

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  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 Byrnes, Edward. "UNC Medical Bulletin Fall 2008" (PDF). Archived from the original (PDF) on 2016-03-04. Retrieved July 19, 2015.
  4. ^ "Escolar, Maria Luisa, MD, MS". Chp.edu. 2013-05-16. Retrieved 2015-07-19.
  5. ^ Riely, Kaitlynn (October 5, 2013). "Pittsburgh's Children's Hospital doctor dedicated to treating those with rare disorders". Pittsburgh Post-Gazette. Archived from the original on February 21, 2015. Retrieved 20 July 2020.
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  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.
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  15. ^ a b "Insights Fall 2011". Insights.pipitonegroup.com. Retrieved 2015-07-19.[permanent dead link‍]
  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 (Dec 2009). "Multidisciplinary management of Hunter's syndrome". Pediatrics. 124 (6): e1228-39. doi:10.1542/peds.2008-0999. PMID 19901005. S2CID 23871763.
  17. ^ Martin H, Poe MD, Reinhartsen D, Pretzel RE, Roush J, Rosenberg A, Dusing SC, Escolar ML (Apr 2007). "Methods for assessing lysosomal storage and related disorders: a multidisciplinary perspective". Acta Paediatr Suppl. 97 (457): 69–75. doi:10.1111/j.1651-2227.2008.00651.x. PMID 18339192. S2CID 5481219.
  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. Archived from the original on 2015-08-01. Retrieved 2015-07-19.
  22. ^ Husain AM; Escolar ML; Kurtzberg J (2006). "Neurophysiologic assessment of mucopolysaccharidosis III". Clin Neurophysiol. 117 (9): 2059–2063. doi:10.1016/j.clinph.2006.05.031. PMID 16884953. S2CID 28156495.
  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 (Mar 2015). "Measurement of psychosine in dried blood spots - a possible improvement to newborn screening programs for Krabbe disease". J Inherit Metab Dis. 38 (5): 923–929. doi:10.1007/s10545-015-9822-z. PMID 25762404. S2CID 6905625.
  24. ^ "Neurodevelopment in Rare Disorders (NDRD): Krabbe Translational Research Network (KTRN)". Ndrdvirtualmed.com. Archived from the original on 2015-07-24. Retrieved 2015-07-19.
  25. ^ "Krabbe Disease KTRN". Tloaf.org. Archived from the original on 2015-05-12. 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 (May 2005). "Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease". N Engl J Med. 352 (20): 2069–81. doi:10.1056/NEJMoa042604. PMID 15901860.
  27. ^ Escolar ML, Yelin K, Poe MD (2006). "Neurodevelopmental outcome of children with infantile Krabbe disease treated with umbilical cord blood transplantation: 10 years of follow up". Lysosomal Storage Dis. 6 (3): 71–9.
  28. ^ Dusing SC, Rosenberg A, Hiemenz JR, Piner S, Escolar M (2005). "Gross and fine motor skills of children with Hurler syndrome (MPS-IH) post umbilical cord blood transplantation: a case series report". Pediatr Phys Ther. 17 (4): 264–7. doi:10.1097/01.pep.0000186510.37581.19. PMID 16357681. S2CID 36379998.
  29. ^ Poe MD, Chagnon SL, Escolar ML (Nov 2014). "Early treatment is associated with improved cognition in Hurler syndrome". Ann Neurol. 76 (5): 747–53. doi:10.1002/ana.24246. PMID 25103575. S2CID 41421103.
  30. ^ Coletti HY, Aldenhoven M, Yelin K, Poe MD, Kurtzberg J, Escolar ML (2015). "Long-term functional outcomes of children with hurler syndrome treated with unrelated umbilical cord blood transplantation". JIMD Rep. JIMD Reports. 20: 77–86. doi:10.1007/8904_2014_395. ISBN 978-3-662-46699-5. PMC 4375128. PMID 25614311.
  31. ^ Dusing SC, Thorpe DE, Mercer VS, Rosenberg AE, Poe MD, Escolar ML (Aug 2007). "Temporal and spatial gait characteristics of children with Hurler syndrome after umbilical cord blood transplantation". Phys Ther. 87 (8): 978–85. doi:10.2522/ptj.20060196. PMID 17553918.
  32. ^ Beam D; Poe M.D; Provenzale JM; Szabolcs P; Martin PL; Prasad VA; Parikh S; Driscoll T; Kurtzberg J; Escolar ML (2007). "Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy". Biol Blood Marrow Transplant. 13 (6): 665–674. doi:10.1016/j.bbmt.2007.01.082. PMID 17531776.
  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 KW (Mar 2012). "Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients". Bone Marrow Transplant. 47 (3): 352–9. doi:10.1038/bmt.2011.99. PMID 21552297. S2CID 10069675.
  34. ^ Buhrman D, Thakkar K, Poe M, Escolar ML (May 2014). "Natural history of Sanfilippo syndrome type A.". J Inherit Metab Dis. 37 (3): 431–7. doi:10.1007/s10545-013-9661-8. PMID 24271936. S2CID 9652582.
  35. ^ Holt JB, Poe MD, Escolar ML (May 2011). "Natural progression of neurological disease in mucopolysaccharidosis type II". Pediatrics. 127 (5): e1258–65. doi:10.1542/peds.2010-1274. PMID 21518713. S2CID 13308507.
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  37. ^ Buhrman D, Thakkar K, Poe M, Escolar ML (2014). "Natural history of Sanfilippo syndrome type A.". J Inherit Metab Dis. 37 (3): 431–7. doi:10.1007/s10545-013-9661-8. PMID 24271936. S2CID 9652582.
  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 (May 2004). "Cord-blood transplants from unrelated donors in patients with hurler's syndrome". N Engl J Med. 350 (19): 1960–9. doi:10.1056/NEJMoa032613. PMID 15128896.
  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 (May 2013). "Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning". Blood. 121 (19): 3981–7. doi:10.1182/blood-2012-09-455238. PMC 3836041. PMID 23493783.
  40. ^ Martin HR, Poe MD, Provenzale JM, Kurtzberg J, Mendizabal A, Escolar ML (Apr 2013). "Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy". Biol Blood Marrow Transplant. 19 (4): 616–24. doi:10.1016/j.bbmt.2013.01.010. PMID 23348427.
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  44. ^ Martin HR, Poe MD, Reinhartsen D, Pretzel RE, Roush J, Rosenberg A, Dusing SC, Escolar ML (Apr 2008). "Methods for assessing neurodevelopment in lysosomal storage diseases and related disorders: a multidisciplinary perspective". Acta Paediatr Suppl. 97 (457): 69–75. doi:10.1111/j.1651-2227.2008.00651.x. PMID 18339192. S2CID 5481219.
  45. ^ Holt J, Poe MD, Escolar ML (Aug 2011). "Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II". J Pediatr. 159 (2): 320–6. doi:10.1016/j.jpeds.2011.03.019. PMID 21530981.
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  47. ^ Sharma A, Fletcher PT, Gilmore JH, Escolar ML, Gupta A, Styner M, Gerig G (2014). "Parametric regression scheme for distributions: Analysis of DTI fiber tract diffusion changes in early brain development". 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI). Vol. 2014. pp. 559–562. doi:10.1109/ISBI.2014.6867932. ISBN 978-1-4673-1961-4. PMC 4209698. PMID 25356194.
  48. ^ Gupta A, Toews M, Janardhana R, Rathi Y, Gilmore J, Escolar M, Styner M (Mar 2013). "Fiber feature map based landmark initialization for highly deformable DTI registration". In Ourselin S, Haynor DR (eds.). Medical Imaging 2013: Image Processing. Proceedings of SPIE. Vol. 8669. pp. 866907–. doi:10.1117/12.2006977. PMC 3864965. PMID 24353392.
  49. ^ Sharma A, Fletcher PT, Gilmore JH, Escolar ML, Gupta A, Styner M, Gerig G (2013). "Spatiotemporal modeling of discrete-time distribution-valued data applied to DTI tract evolution in infant neurodevelopment". Proc IEEE Int Symp Biomed Imaging. 2013: 684–687. doi:10.1109/ISBI.2013.6556567. PMC 3892706. PMID 24443688.
  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, Styner MA (2013). "Diffusion imaging quality control via entropy of principal direction distribution". NeuroImage. 82: 1–12. doi:10.1016/j.neuroimage.2013.05.022. PMC 3798052. PMID 23684874.
  51. ^ Wang Y, Gupta A, Liu Z, Zhang H, Escolar ML, Gilmore JH, Gouttard S, Fillard P, Maltbie E, Gerig G, Styner M (Apr 2011). "DTI registration in atlas based fiber analysis of infantile Krabbe disease". NeuroImage. 55 (4): 1577–86. doi:10.1016/j.neuroimage.2011.01.038. PMC 3062693. PMID 21256236.
  52. ^ Fan Z, Styner M, Muenzer J, Poe MD, Escolar ML (Aug 2010). "Correlation of automated volumetric analysis of brain MR imaging with cognitive impairment in a natural history study of mucopolysaccharidosis II". AJNR Am J Neuroradiol. 31 (7): 1319–23. doi:10.3174/ajnr.A2032. PMC 7965470. PMID 20203116.
  53. ^ Provenzale JM, Peddi S, Kurtzberg J, Poe MD, Mukundan S, Escolar M (Jan 2009). "Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's disease". AJR Am J Roentgenol. 192 (1): 59–65. doi:10.2214/AJR.07.3885. PMID 19098180.
  54. ^ Provenzale JM, Escolar M, Kurtzberg J (Dec 2005). "Quantitative analysis of diffusion tensor imaging data in serial assessment of Krabbe disease". Ann N Y Acad Sci. 1064 (1): 220–9. Bibcode:2005NYASA1064..220P. doi:10.1196/annals.1340.040. PMID 16394159. S2CID 7103301.
  55. ^ McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM (2005). "Krabbe Disease Treated with Hematopoietic Stem Cell Transplantation: Serial Assessment of Anisotropy Measurements—Initial Experience". Radiology. 236 (1): 221–230. doi:10.1148/radiol.2353040716. PMID 15987975.
  56. ^ Escolar ML, Poe MD, Smith JK, Gilmore JH, Kurtzberg J, Lin W, Styner M (May 2009). "Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease". AJNR Am J Neuroradiol. 30 (5): 1017–21. doi:10.3174/ajnr.A1476. PMC 2763775. PMID 19386732.
  57. ^ Gupta A, Poe MD, Styner MA, Panigrahy A, Escolar ML (Sep 2014). "Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease". NeuroImage Clin. 7: 792–8. doi:10.1016/j.nicl.2014.09.014. PMC 4375637. PMID 25844309.
  58. ^ Zuccoli G, Narayanan S, Panigrahy A, Poe MD, Escolar ML (2015). "Midbrain morphology reflects extent of brain damage in Krabbe disease". Neuroradiology. 57 (7): 739–745. doi:10.1007/s00234-015-1523-7. PMID 25859833. S2CID 6349697.
  59. ^ "NDRD Training Program". Chp.edu. 2013-07-25. Retrieved 2015-07-19.
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  62. ^ "International Collaborations". Chp.edu. 2014-10-28. Retrieved 2015-07-19.
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