Browsing by Author "Spiridigliozzi, Gail A"

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    Behavioral, social and school functioning in children with Pompe disease
    (Molecular Genetics and Metabolism Reports, 2020-12) Korlimarla, Aditi; Spiridigliozzi, Gail A; Stefanescu, Mihaela; Austin, Stephanie L; Kishnani, Priya S
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    Challenges in measuring the effects of pharmacological interventions on cognitive and adaptive functioning in individuals with Down syndrome: A systematic review.
    (American journal of medical genetics. Part A, 2017-11) Keeling, Lori A; Spiridigliozzi, Gail A; Hart, Sarah J; Baker, Jane A; Jones, Harrison N; Kishnani, Priya S
    We systematically reviewed the measures used in pharmaceutical trials in children/adults with Down syndrome without dementia. Our purpose was to identify developmentally appropriate outcome measures capable of detecting changes in cognitive and adaptive functioning in this population. Eleven studies were included and used diverse outcome measures across the domains of language, memory, attention, behavior, and executive/adaptive functioning. Our results highlight the challenges in selecting measures capable of capturing improvements in pharmaceutical trials in individuals with DS. We offer suggestions to enhance future research, including: conducting studies with larger samples of participants with a range of developmental abilities; modifying existing/developing novel outcome measures; incorporating advances from related areas and DS observational studies; and considering alternative analytic techniques to characterize treatment effects.
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    Early cognitive development in children with infantile Pompe disease.
    (Molecular genetics and metabolism, 2012-03) Spiridigliozzi, Gail A; Heller, James H; Case, Laura E; Jones, Harrison N; Kishnani, Priya S
    This report describes the cognitive development of 17 children with infantile Pompe disease who participated in a 52-week clinical trial of enzyme replacement therapy (ERT) via biweekly infusion of Myozyme® (alglucosidase alfa). Subjects were six months of age or younger (adjusted for gestational age) upon initiation of ERT. The Mental Scale of the Bayley Scales of Infant Development-Second Edition (BSID-II) was administered to obtain a Mental Development Index (MDI) at baseline and weeks 12, 26, 38, and 52 of ERT to assess cognitive development in this treated cohort. Data regarding motor development were also obtained at the same visits and these were used to determine correlations between cognitive and motor development. Over the course of the study, two subgroups of subjects emerged: high responders who were sitting independently and/or ambulating by week 52 (n=13) and limited responders who showed minimal motor gains throughout the first year of ERT (n=4). In the high responder group, MDI scores on the BSID-II remained stable throughout the study and were within normal limits. Positive correlations between cognitive and motor development were also present. These data suggest that the cognitive function of infants up to 18 months of age with Pompe disease is unaffected by the possible presence of glycogen in the central nervous system. Continued investigation of the cognitive development of older survivors is warranted.
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    Novel approaches to quantify CNS involvement in children with Pompe disease.
    (Neurology, 2020-06-09) Korlimarla, Aditi; Spiridigliozzi, Gail A; Crisp, Kelly; Herbert, Mrudu; Chen, Steven; Malinzak, Michael; Stefanescu, Mihaela; Austin, Stephanie L; Cope, Heidi; Zimmerman, Kanecia; Jones, Harrison; Provenzale, James M; Kishnani, Priya S
    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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    Safety and efficacy of rivastigmine in adolescents with Down syndrome: long-term follow-up.
    (J Child Adolesc Psychopharmacol, 2010-12) Heller, James H; Spiridigliozzi, Gail A; Crissman, Blythe G; McKillop, Jane Anne; Yamamoto, Haru; Kishnani, Priya S
    Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects.