Novel approaches to quantify CNS involvement in children with Pompe disease.


OBJECTIVE:To characterize the extent of central nervous system involvement in children with Pompe disease using brain magnetic resonance imaging (MRI) and developmental assessments. METHODS:The study included fourteen children (ages 6-18 years) with infantile Pompe disease (IPD) (n=12) or late onset Pompe disease (LOPD) (n=2) receiving enzyme replacement therapy. White matter (WM) hyperintense foci seen in the brain MRIs were systematically quantified using the Fazekas scale (FS) grading system with a novel approach; the individual FS scores from ten anatomical areas were summed to yield a total FS score (range: absent-0 to severe-30) for each child. The FS scores were compared to developmental assessments of cognition and language obtained during the same time period. RESULTS:Mild to severe WM hyperintense foci were seen in 10/12 children with IPD (median age-10.6 years) with total FS scores ranging from 2 to 23. Periventricular, subcortical and deep WM were involved. WM hyperintense foci were seen throughout the path of the corticospinal tracts in the brain in children with IPD. Two children with IPD had no WM hyperintense foci. Children with IPD had relative weaknesses in Processing Speed, Fluid Reasoning, Visual Perception, and receptive vocabulary. The two children with LOPD had no WM hyperintense foci, and high scores on most developmental assessments. CONCLUSION:This study systematically characterized WM hyperintense foci in children with IPD; which could serve as a benchmark for longitudinal follow up of WM abnormalities in patients with Pompe disease and other known neurodegenerative disorders or leukodystrophies in children.






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Publication Info

Korlimarla, Aditi, Gail A Spiridigliozzi, Kelly Crisp, Mrudu Herbert, Steven Chen, Michael Malinzak, Mihaela Stefanescu, Stephanie L Austin, et al. (2020). Novel approaches to quantify CNS involvement in children with Pompe disease. Neurology. pp. 10.1212/WNL.0000000000009979–10.1212/WNL.0000000000009979. 10.1212/wnl.0000000000009979 Retrieved from

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Gail A. Spiridigliozzi

Professor in Psychiatry and Behavioral Sciences

Cholinergic therapy in children and adolescents with Down syndrome; premutation carriers of fragile X syndrome; cognitive development of children with infantile-onset Pompe disease who are being treated with enzyme replacement therapy.


Kanecia Obie Zimmerman

Professor of Pediatrics

Harrison N. Jones

Associate Professor of Head and Neck Surgery & Communication Sciences

James Michael Provenzale

Professor of Radiology

I have the following major research areas:
I. Diffusion tensor imaging (an MR technique that measures rate and direction of microscopic water motion) to examine white matter pathways in the brain. This technique is used by many investigators in an attempt to understand white matter microstructure. My recent work has centered on the histological correlation of DTI metrics. In addition, because DTI metrics can vary substantially within a single scanner at multiple time points as well as between scanners, my work is focused on understanding causes of such variability and designing methods to decrease it. 
Since 1998, I have mentored third-year students at Duke University School of Medicine (typically one medical student per year) in both DTI research and perfusion imaging research. Although the research techniques are highly advanced, our implementation of various "user-friendly" software programs allows students with little or no prior experience to analyze data in a productive manner. Our research is also well-suited to individuals with advanced computer skills or an interest in biomedical or electrical engineering. Students work closely with research personnel on a daily basis. They also meet with collaborators from various basic science and clinical departments and me in a laboratory meeting once a week. The focus of these meetings is to plan experiments, refine research methods, discuss experimental results and prepare manuscripts. Students serve as first authors or co-authors on manuscripts based on their specific research project. The results of a number of such projects have been published.

II. Applications of nanotechnology to treatment of cancer (both CNS and non-CNS) and brain disorders. My research involves design and implementation of nanoparticles and fluorescent molecules for cancer diagnosis and therapy. Although I am trained as a neurologist and neuroradiologist, most of my nanotechnology-based research is oriented towards non-CNS tumors such as breast cancer and sarcomas. In the past few years, my Emory and Georgia Tech colleagues and I have conducted research using animals with naturally-occurring tumors at the University of Georgia College of Veterinary Medicine. This work has focused on the use of a handheld device to detect fluorophores that are administered intravenously prior to surgery. We are presently validating the use of this combination of imaging device and contrast agent to guide surgical resection of tumors. I am also interested in development of nanotechnology-based non-invasive and minimally invasive devices that can continuously monitor tumor physiological characteristics and response to therapy. This work is done in conjunction with a number of colleagues in Biomedical Engineering at both Duke and Emory and supported by a number of NIH grants. Finally, I have a strong interest in use of nanotechnology for tissue engineering and regenerative medicine. 


Priya Sunil Kishnani

Chen Family Distinguished Professor of Pediatrics


A multidisciplinary approach to care of individuals with genetic disorders in conjunction with clinical and bench research that contributes to:
1) An understanding of the natural history and delineation of long term complications of genetic disorders  with a special focus on liver Glycogen storage disorders, lysosomal disorders with a special focus on Pompe disease, Down syndrome and hypophosphatasia
2) ) The development of new therapies such as AAV gene therapy, enzyme therapy, small molecule and other approaches for genetic disorders through translational research

3) The development and execution of large multicenter trials to confirm safety and efficacy of potential therapies
4) Role of antibodies/immune response in patients on therapeutic proteins and AAV gene therapy

. Glycogen Storage Disease (GSD): We are actively following subjects with all types of Glycogen Storage Disease, with particular emphasis on types I, II, III, IV, VI and IX. The goal of the treatment team is to better determine the clinical phenotype and long term complications of these diseases. Attention to disease manifestations observed in adulthood, such as adenomas and risk for HCC, is of paramount importance in monitoring and treating these chronic illnesses. We are establishing clinical algorithms for managing adenomas, and the overall management of these patients including cardiac, bone, muscle and liver issues. A special focus is biomarker discovery, an Omics approach including metabolomics and immune phenotyping. We are working on AAV gene therapy for several hepatic GSDs

.Lysosomal Storage Disease: The Duke Lysosomal Storage Disease (LSD) treatment center follows and treats patients with Pompe, Gaucher, Fabry, Mucopolysaccharidosis, Niemann Pick, LAL-D and other LSD's. The Duke Metabolism Clinical Research Team is exploring many aspects of enzyme replacement therapy (ERT), including impact on different systems, differential response, and long term effects. Other symptomatic and treatment interventions for this category of diseases are also being explored in the context of clinical care.

. Pompe Disease: The care team has extensive experience in the care of infants and adults with Pompe disease and was instrumental in conducting clinical trials and the bench to bedside work that led to the 2006 FDA approval of alglucosidase alfa, the first treatment for this devastating disease. We are currently focusing on role of antibodies/immune response on patient outcome and role of immune modulation/immune suppression as an adjunct to ERT. Our team is also working on AAV gene therapy for Pompe disease. A focus is on newborn screening (NBS) and understanding the clinical phenotype and management approaches for babies identified via NBS

.  Hypophosphatasia: We follow a large cohort of patients with HPP. The goal is to understand the features of the disease beyond bone disease, development of biomarkers, role of ERT and immune responses in HPP

. Neuromuscular disorders: We are collaborating with neurologists, cardiologists and neuromuscular physicians to serve as a treatment site for clinical trials in these diseases. We are currently involved in trials of DMD and are working closely on setting up collaborations for studies in SMA.

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