title: The cerebro-morphological fingerprint of a progeroid syndrome: white matter changes correlate with neurological symptoms in xeroderma pigmentosum.
abstract: BACKGROUND
  Xeroderma pigmentosum (XP) is a rare autosomal recessive progeroid syndrome. It has recently been shown that the underlying DNA repair defect plays a central role in the aging process. In addition to skin symptoms, various premature neurological abnormalities have been reported.
  
  
  RESULTS
  We present the clinical neurological phenotype in 14 XP patients (seven subtypes), in seven of these patients together with conventional and multiparametric advanced MRI data to assess the macrostructural and microstructural cerebral morphology in comparison to controls, including volumetric measurements, MR spectroscopy ((1)H MRS), and diffusion tensor imaging (DTI). Clinical hallmarks were spinocerebellar ataxia, pyramidal tract signs, and mild cognitive deficits. DTI demonstrated significantly reduced WM directionality in all regions investigated, i.e. the thalamus, the corticospinal tracts and the dorsal corpus callosum. Single patients showed a marked relative hippocampal volume reduction, but the patients were not different from controls in the volumetric measurements of hippocampal and whole brain volumes at group level. However, (1)H MRS demonstrated that the hippocampal formation was metabolically altered.
  
  
  CONCLUSIONS
  The most prominent feature was the white matter affectation, as assessed by DTI, with volume and directionality reductions of the fiber projections involving both the craniocaudal fibers and the interhemispheric connections. These findings, although heterogeneous among the study sample, could be correlated with the clinico-neurological symptoms. The imaging findings support the position that myelin structures degrade prematurely in the brain of XP patients.
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany. jan.kassubek@uni-ulm.de
authors.forename: Jan
authors.initials: J
authors.lastname: Kassubek
authors.forename: Anne-Dorte
authors.initials: AD
authors.lastname: Sperfeld
authors.forename: Elmar H
authors.initials: EH
authors.lastname: Pinkhardt
authors.forename: Alexander
authors.initials: A
authors.lastname: Unrath
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Müller
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Mark
authors.initials: M
authors.lastname: Berneburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016880:Anisotropy; D016022:Case-Control Studies; D054022:Cerebrum / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D056324:Diffusion Tensor Imaging; D005260:Female; D006184:Habits; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011371:Progeria / Q000150:complications* / Q000473:pathology*; D012727:Sex Characteristics; D013577:Syndrome; D013788:Thalamus / Q000473:pathology; D014983:Xeroderma Pigmentosum / Q000150:complications* / Q000473:pathology*; D055815:Young Adult