About

Amy Tara Waldman, M.D., M.S.C.E., is an Associate Professor of Neurology at the Children's Hospital of Philadelphia. She serves as Medical Director of the Leukodystrophy Center of Excellence and as Associate Director of Neurology Gene Therapy at the same institution. Her educational background includes a B.A. in Chemistry from Johns Hopkins University, an M.D. from Jefferson Medical College, and an M.S.C.E. in Epidemiology from the Perelman School of Medicine at the University of Pennsylvania. Dr. Waldman’s professional focus is on neurology, with a particular emphasis on leukodystrophies and neurogenetic disorders. Her research contributions include studies on clinical phenotypes, gene therapy outcomes, and neurodegeneration, with publications addressing topics such as Alexander disease, retinal vasculopathy, and the safety and efficacy of gene therapies. She is actively involved in advancing understanding and treatment of neurological conditions affecting children, contributing to both clinical and translational research efforts.

Research topics

• Psychology
• Psychiatry
• Pediatrics
• Medicine
• Developmental psychology

Selected publications

• Severe retinal vasculopathy associated with myelin oligodendrocyte glycoprotein antibody optic neuritis in a toddler

  Journal of American Association for Pediatric Ophthalmology and Strabismus · 2026-03-25

  article
  PublisherDOI

• Paediatric cerebrospinal fluid immune profiling distinguishes paediatric-onset multiple sclerosis from other paediatric-onset acute neurological disorders

  EBioMedicine · 2026-01-01

  articleOpen access

  BACKGROUND: The cerebrospinal fluid (CSF) provides a unique glimpse into the central nervous system (CNS) compartment and offers insights into immune processes associated with both healthy immune surveillance as well as inflammatory disorders of the CNS. The latter include demyelinating disorders, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), that warrant different therapeutic approaches yet are not always straightforward to distinguish on clinical and imaging grounds alone. METHODS: We established a comprehensive phenotypic landscape of the paediatric CSF immune compartment across a range of non-inflammatory and inflammatory neurological disorders, with a focus on better elucidating CNS-associated immune mechanisms potentially involved in, and discriminating between, paediatric-onset MS (MS) and other paediatric-onset suspected neuroimmune disorders, including MOGAD. FINDINGS: CSF from paediatric patients with non-inflammatory neurological disorders is primarily composed of non-activated CD4+ T cells, with few if any B cells present. CSF from paediatric patients with acquired inflammatory demyelinating disorders is characterised by increased numbers of B cells compared to CSF of both patients with other inflammatory or non-inflammatory conditions. Certain features, including particular increased frequencies of antibody-secreting cells (ASCs) and decreased frequencies of CD14+ myeloid cells, distinguish MS from MOGAD and other acquired demyelinating syndromes. INTERPRETATION: Increased CSF ASC frequencies and decreased CSF CD14+ myeloid cell frequencies help distinguish paediatric-onset MS from paediatric-onset MOGAD and other acquired demyelinating syndromes. Our findings provide insight into CNS-associated immune mechanisms that may be present early in the clinical course of MS. FUNDING: Stated in acknowledgements section of manuscript.

  PublisherDOI

• Role of Tocilizumab in Severe CNS Inflammatory Presentations in Children

  Neurology · 2026-04-07 · 1 citations

  articleOpen access

  OBJECTIVES: Anti-interleukin 6 receptor (anti-IL6R) therapies have been proven to reduce relapse rates in patients with neuromyelitis optica spectrum disorder and are under investigation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). One anti-IL6R therapy, tocilizumab (TCZ), has been reported as a treatment option in cases of life-threatening MOGAD attacks. The aim of this study was to further evaluate the safety and effectiveness of IV-TCZ for acute and severe CNS inflammatory events in children. METHODS: This retrospective study reviewed medical records of children younger than 18 years treated with IV-TCZ for acute-severe CNS inflammation at the Children's Hospital of Philadelphia between 2022 and 2025, excluding those with new-onset refractory status epilepticus without evidence of CNS inflammation. Clinical features, imaging, serum and CSF profiles, treatments, and outcomes were assessed, with primary evaluation of TCZ response within 72 hours postadministration. RESULTS: Eleven patients were included, of whom 8 demonstrated clinical improvement within 72 hours of IV-TCZ administration. Outcomes included rapid intracranial pressure reduction, recovery in relapsing optic neuritis and myelitis, and improvement in RANBP2-related acute necrotizing encephalopathy. No acute adverse effects were observed. One patient died despite immunotherapy. CSF cytokine panels showed elevated IL-6 in 5 patients, with normal serum IL-6 concentrations. Three of the 5 showed a response to TCZ. DISCUSSION: TCZ may offer potential benefit in select neuroinflammatory conditions, although clinical trials are needed to confirm its efficacy and guide use in such scenarios. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that TCZ improves clinical outcomes in children with acute-severe CNS inflammatory events.

  PublisherOA PDFDOI

• Factors Influencing Early and Late B-Cell Repopulation After Rituximab Therapy in Pediatric Central Nervous System Inflammatory Disorders

  Pediatric Neurology · 2026-04-03

  article
  PublisherDOI

• Diagnosing Alexander disease in adults

  Practical Neurology · 2025-05-11 · 1 citations

  reviewOpen accessSenior author

  ) gene. Its presenting symptoms often differ according to age at onset. Although Alexander disease typically presents in young children with seizures and developmental delays, its presentation in adults may include bulbar signs, ataxia and autonomic dysfunction. Because of the heterogeneous and non-specific symptoms associated with adult-onset Alexander disease, the diagnosis typically requires comprehensive clinical and neuroimaging evaluation as well as confirmatory genetic testing. Here, we present detailed case descriptions of patients who first presented with symptoms of Alexander disease as adults, with guidance on recognising distinctive clinical and radiological characteristics associated with the later-onset form. Timely recognition and referral of patients with Alexander disease will enable earlier interventions that may mitigate disease severity or slow disease progression if such interventions become available.

  PublisherOA PDFDOI

• Bi-allelic variants in BCAT1 impair mitochondrial function and are associated with a candidate neurometabolic disorder

  Human Genetics and Genomics Advances · 2025-10-01

  articleOpen access

  Branched-chain amino acid transaminase-1 (BCAT1) initiates the catabolism of branched-chain amino acids (BCAAs), which are essential for neurologic function. However, the role of BCAT1 in neurodevelopment is largely unknown. Here, we identify compound heterozygous BCAT1 variants in a patient with a severe progressive neurodevelopmental syndrome. To investigate the functional consequences, we established patient variant (BCAT1: c.792T>A p.Phe264Leu; c.1042G>A p.Glu348Lys) and BCAT1 knockout hiPSC models. Both disease models show profound defects in cortical neuron differentiation and neurite outgrowth. Furthermore, metabolic analysis revealed evidence of mitochondrial dysfunction associated with increased levels of tricarboxylic acid (TCA) cycle intermediates, glutamate, and glutamine. This increase is linked to altered oxygen consumption rates, superoxide production, and upregulation of UCP2 in BCAT1 disease neurons, suggesting a downstream impact on electron transport chain homeostasis. These findings establish a regulatory role for BCAT1 in mitochondrial function and further define a role for genomic variants in BCAT1 in neurometabolic disorders.

  PublisherDOI

• Language Skills in Patients With Alexander Disease

  American Journal of Speech-Language Pathology · 2025-11-18

  articleOpen accessSenior author

  Purpose: This study aimed to investigate the language skills of children with Alexander disease (AxD) and determine whether disease subtypes and/or age contributes to variability in language performance. Method: Eighty-two participants with AxD, confirmed by GFAP testing, were enrolled, and the disease phenotype was determined using clinical and imaging features (56 cerebral, nine intermediate, and 17 bulbospinal). The participants' language abilities were assessed using the Preschool Language Scale–Fifth Edition (PLS-5), the Clinical Evaluation of Language Fundamentals–Fifth Edition (CELF-5), and the Peabody Picture Vocabulary Test–Fourth Edition (PPVT-4), based on the patient's age and linguistic level. The Communication Function Classification System was also used to determine functional communication abilities. Wilcoxon signed-ranks test or Kruskal–Wallis test was used to determine differences across groups. Results: The mean PLS-5 Total Language Score (TLS) was 70.10 ( SD = 17.62). Performance on the CELF-5 varied by phenotype (Core Language Score [CLS]: cerebral, M = 57.22, SD = 19.89; intermediate, M = 92.50, SD = 20.54; bulbospinal, M = 91.56, SD = 19.51). PLS-5 performance was negatively correlated with age at the first research study visit for cerebral participants (TLS: rho = −.367, p = .017). CELF-5 and PPVT-4 scores, on the other hand, were not correlated with age at first visit but with age at first neurological symptom (CLS: rho = .576, p = .003; PPVT-4: rho = .336, p = .011). Conclusions: Cerebral patients demonstrated significant language deficits, whereas intermediate and bulbospinal subjects displayed stronger abilities, with deficits in some patients. These implications can be used to determine the functional impact of communication deficits and to provide accommodations and interventions in the treatment plans of patients with AxD.

  PublisherOA PDFDOI

• Factors influencing early and late B-cell repopulation after Rituximab therapy in pediatric CNS inflammatory disorders

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Epigenetic age and telomere length correlations in pediatric-onset multiple sclerosis

  Multiple Sclerosis Journal · 2025-11-06

  articleOpen access

  Background: Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes. Objectives: To determine the correlation between DNAm and TL aging markers. Methods: We conducted a cross-sectional case–control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL. Results: We analyzed biological ages in 270 participants (125 POMS, mean 15.7 years; 145 controls, mean 15.3 years). There were moderate correlations among the different DNAm clocks, but no correlations between DNAm clocks and TL in pooled analyses. In a stratified analysis, only the control group showed a modest correlation between TL and PhenoAge clock ( r = 0.2, p = 0.06). Conclusions: DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.

  PublisherDOI

• Allele-specific vitamin D receptor binding is associated with pediatric-onset multiple sclerosis

  Multiple Sclerosis Journal - Experimental Translational and Clinical · 2025-04-01

  articleOpen access

  Background and Objectives: The genetic basis of adult-onset multiple sclerosis (MS) is well-studied, but less is known about pediatric-onset MS (pedMS), comprising approximately 5% of all MS onsets. Mendelian randomization (MR) studies have demonstrated evidence for a causal association between MS and both 25-hydroxyvitamin D [25(OH)D] serum levels and genetic variation related to vitamin D receptor (VDR) binding. The objective was to identify whether VDR binding variants (VDR-BVs) previously implicated in adult-onset MS were associated with pedMS using genetic instrumental variables (GIVs). Methods: Using previously identified VDR-BVs to construct individual GIVs with two-sample MR, we investigated associations with pedMS in 725 cases and 592 controls of European ancestry from the US Network of Pediatric MS Centers. Associations between each VDR-BV and pedMS were estimated using logistic regression adjusting for the first three genome-wide principal components. A significant interaction between a VDR-BV and 25(OH)D GIV provided evidence for a causal association unbiased by pleiotropy. Results: One VDR-BV, rs2531804, previously associated with adult-onset MS, was also significantly associated with pedMS after multiple testing correction. Discussion: This study is the first to use VDR-BVs from previous MR studies to demonstrate causal differences in VDR binding at a locus contributing to pedMS susceptibility.

  PublisherDOI

Recent grants

• Development of visual and neurologic outcome measures in pediatric MS

  NIH · $924k · 2012–2017

Frequent coauthors

• Brenda Banwell

  Children's Hospital of Philadelphia

  500 shared

• Mark Gorman

  428 shared

• Leslie Benson

  Boston Children's Hospital

  357 shared

• Gülay Alper

  University of Pittsburgh

  326 shared

• Russell C. Dale

  Antioch University Seattle

  325 shared

• Kumaran Deiva

  Witten/Herdecke University

  320 shared

• Fabienne Brilot

  University of Sydney

  320 shared

• Catherine J. Riney

  Queensland Children’s Hospital

  320 shared