title: Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression.
abstract: OBJECTIVE
  Experimental therapies for ceroid lipofuscinosis, neuronal, 2 (CLN2), a genetic disorder of childhood associated with progressive brain atrophy, are currently being developed. Because quantitative descriptions of the natural course of brain volume loss are needed to evaluate novel therapies, we performed MR imaging volumetry of patients with CLN2 to identify a suitable MR imaging marker of disease progression.
  
  
  METHODS
  Thirteen patients (8 females, 5 males) were recruited from a prospective natural disease cohort of patients with neuronal ceroid lipofuscinosis. Repeated MR imaging volumetric analysis (29 datasets) was performed by using the FreeSurfer Software Suite. Follow-up time ranged from 8 months to 5.3 years. MR imaging-segmented brain volumes were correlated to patient age and clinical scores.
  
  
  RESULTS
  Segmented brain volumes correlated significantly with patient age (lateral ventricles,r= 0.606,P= .001; supratentorial cortical GM,r= -0.913,P< .001; supratentorial WM,r= -0.865,P< .001; basal ganglia/thalamus,r= -0.832,P< .001; cerebellar GM,r= -0.659,P< .001; cerebellar WM,r= -0.830,P< .001) and clinical scores (lateral ventricles,r= -0.692,P< .001; supratentorial cortical GM,r= 0.862,P< .001; supratentorial WM,r= 0.735,P< .001; basal ganglia/thalamus,r= 0.758,P< .001; cerebellar GM,r= 0.609,P= .001; cerebellar WM,r= 0.638,P< .001). Notably, supratentorial cortical GM showed a uniform decline across the patient cohort. During late stages of the disease when the clinical score was zero, segmented brain volumes still correlated with patient age; this finding suggests that MR imaging volumetry allows quantitative assessment of disease progression at stages when it cannot be detected by clinical assessment alone.
  
  
  CONCLUSIONS
  Automated MR imaging volumetry, as a nonsubjective and highly sensitive tool, is feasible in CLN2 disease and provides a quantitative basis to evaluate novel experimental therapies.
authors.affiliation: From the Departments of Diagnostic and Interventional Neuroradiology (U.L., J.S., J.F.) u.loebel@uke.de.
authors.forename: U
authors.identifier: http://orcid.org/0000-0001-9844-3464
authors.initials: U
authors.lastname: Löbel
authors.affiliation: From the Departments of Diagnostic and Interventional Neuroradiology (U.L., J.S., J.F.).
authors.forename: J
authors.identifier: http://orcid.org/0000-0003-3125-1083
authors.initials: J
authors.lastname: Sedlacik
authors.affiliation: Pediatrics (M.N., A.K., A.S.).
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-1870-1142
authors.initials: M
authors.lastname: Nickel
authors.affiliation: Medical Biometry and Epidemiology (S.L.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-4832-4333
authors.initials: S
authors.lastname: Lezius
authors.affiliation: From the Departments of Diagnostic and Interventional Neuroradiology (U.L., J.S., J.F.).
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-8533-7478
authors.initials: J
authors.lastname: Fiehler
authors.affiliation: Department of Pediatrics (I.N.), University of Minnesota, Minneapolis, Minnesota.
authors.forename: I
authors.identifier: http://orcid.org/0000-0002-3833-1484
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: Pediatrics (M.N., A.K., A.S.).
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-2700-0401
authors.initials: A
authors.lastname: Kohlschütter
authors.affiliation: Pediatrics (M.N., A.K., A.S.).
authors.forename: A
authors.identifier: http://orcid.org/0000-0001-9156-4861
authors.initials: A
authors.lastname: Schulz