title: Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease).
abstract: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease.
  
  
  
  Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness.
  
  
  
  An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres).
  
  
  
  This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression.
authors.affiliation: From the Departments of Radiology (J.P.D., H.U.V., L.A.H., D.B.) jpd2001@med.cornell.edu.
authors.forename: J P
authors.identifier: 0000-0001-7170-488X
authors.initials: JP
authors.lastname: Dyke
authors.affiliation: Genetic Medicine (D.S., C.H., D.M., S.M.K., R.G.C., D.B.).
authors.forename: D
authors.identifier: 0000-0002-2218-5910
authors.initials: D
authors.lastname: Sondhi
authors.affiliation: From the Departments of Radiology (J.P.D., H.U.V., L.A.H., D.B.).
authors.forename: H U
authors.identifier: 0000-0003-2811-2074
authors.initials: HU
authors.lastname: Voss
authors.affiliation: Pediatrics (K.Y., B.K.).
authors.forename: K
authors.identifier: 0000-0001-5560-3392
authors.initials: K
authors.lastname: Yohay
authors.affiliation: Genetic Medicine (D.S., C.H., D.M., S.M.K., R.G.C., D.B.).
authors.forename: C
authors.identifier: 0000-0001-7392-5758
authors.initials: C
authors.lastname: Hollmann
authors.affiliation: Genetic Medicine (D.S., C.H., D.M., S.M.K., R.G.C., D.B.).
authors.forename: D
authors.identifier: 0000-0001-8920-1631
authors.initials: D
authors.lastname: Mancenido
authors.affiliation: Genetic Medicine (D.S., C.H., D.M., S.M.K., R.G.C., D.B.).
authors.forename: S M
authors.identifier: 0000-0003-1869-834X
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: From the Departments of Radiology (J.P.D., H.U.V., L.A.H., D.B.).
authors.forename: L A
authors.identifier: 0000-0001-5519-9326
authors.initials: LA
authors.lastname: Heier
authors.affiliation: Division of Biostatistics (K.D.R.), Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minnesota.
authors.forename: K D
authors.identifier: 0000-0001-9968-0090
authors.initials: KD
authors.lastname: Rudser
authors.affiliation: Pediatrics (K.Y., B.K.).
authors.forename: B
authors.identifier: 0000-0001-6360-343X
authors.initials: B
authors.lastname: Kosofsky
authors.affiliation: Psychiatry (B.J.C.), Weill Cornell Medical College, New York, New York.
authors.forename: B J
authors.identifier: 0000-0003-2905-9834
authors.initials: BJ
authors.lastname: Casey
authors.affiliation: Genetic Medicine (D.S., C.H., D.M., S.M.K., R.G.C., D.B.).
authors.forename: R G
authors.identifier: 0000-0001-6177-6839
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: From the Departments of Radiology (J.P.D., H.U.V., L.A.H., D.B.) Genetic Medicine (D.S., C.H., D.M., S.M.K., R.G.C., D.B.).
authors.forename: D
authors.identifier: 0000-0002-7162-9020
authors.initials: D
authors.lastname: Ballon
mesh_terms: D001921:Brain / Q000473:pathology*; D002648:Child; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000473:pathology*; D012189:Retrospective Studies; D000091346:Tripeptidyl-Peptidase 1
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