title: MRI Brain Volume Measurements in Infantile Neuronal Ceroid Lipofuscinosis.
abstract: Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase 1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury, resulting in rapid neurodegeneration and childhood death. As part of a project studying the treatment benefits of a combination of cysteamine bitartrate andN-acetyl cysteine, we made serial measurements of patients' brain volumes with MR imaging.
  
  
  
  Ten patients with infantile neuronal ceroid lipofuscinosis participating in a treatment/follow-up study underwent brain MR imaging that included high-resolution T1-weighted images. After manual placement of a mask delineating the surface of the brain, a maximum-likelihood classifier was applied to determine total brain volume, further subdivided as cerebrum, cerebellum, brain stem, and thalamus. Patients' brain volumes were compared with those of a healthy population.
  
  
  
  Major subdivisions of the brain followed similar trajectories with different timing. The cerebrum demonstrated early, rapid volume loss and may never have been normal postnatally. The thalamus dropped out of the normal range around 6 months of age; the cerebellum, around 2 years of age; and the brain stem, around 3 years of age.
  
  
  
  Rapid cerebral volume loss was expected on the basis of previous qualitative reports. Because our study did not include a nontreatment arm and because progression of brain volumes in infantile neuronal ceroid lipofuscinosis has not been previously quantified, we could not determine whether our intervention had a beneficial effect on brain volumes. However, the level of quantitative detail in this study allows it to serve as a reference for evaluation of future therapeutic interventions.
authors.affiliation: From the Department of Radiology and Imaging Sciences (E.H.B.), Clinical Center, National Institutes of Health, Bethesda, Maryland bakere@mail.nih.gov.
authors.forename: E H
authors.identifier: 0000-0001-7347-2170
authors.initials: EH
authors.lastname: Baker
authors.affiliation: Program on Endocrinology and Molecular Genetics (S.W.L., Z.Z., A.B.M.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: S W
authors.identifier: 0000-0002-5031-7909
authors.initials: SW
authors.lastname: Levin
authors.affiliation: Program on Endocrinology and Molecular Genetics (S.W.L., Z.Z., A.B.M.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Z
authors.identifier: 0000-0001-7037-5420
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Program on Endocrinology and Molecular Genetics (S.W.L., Z.Z., A.B.M.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: A B
authors.identifier: 0000-0003-4445-5464
authors.initials: AB
authors.lastname: Mukherjee
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000375:Aging / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging*; D001933:Brain Stem / Q000000981:diagnostic imaging; D002531:Cerebellum / Q000000981:diagnostic imaging; D054022:Cerebrum / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D003543:Cysteamine / Q000627:therapeutic use; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000000981:diagnostic imaging* / Q000188:drug therapy; D013788:Thalamus / Q000000981:diagnostic imaging
chemical_list: D003543:Cysteamine; D000111:Acetylcysteine