title: Neuroimaging supports central pathology in familial dysautonomia.
abstract: Familial dysautonomia (FD) is a hereditary peripheral and central nervous system disorder with poorly defined central neuropathology. This prospective pilot study aimed to determine if MRI would provide objective parameters of central neuropathology. There were 14 study subjects, seven FD individuals (18.6 +/- 4.2 years, 3 female) and seven controls (19.1 +/- 5.8 years, 3 female). All subjects had standardized brain MRI evaluation including quantitative regional volume measurements, diffusion tensor imaging (DTI) for assessment of white matter (WM) microstructural integrity by calculation of fractional anisotropy (FA), and proton MR spectroscopy ((1)H MRS) to assess neuronal health. The FD patients had significantly decreased FA in optic radiation (p = 0.009) and middle cerebellar peduncle (p = 0.004). Voxel-wise analysis identified both GM and WM microstructural damage among FD subjects as there were nine clusters of WM FA reductions and 16 clusters of GM apparent diffusion coefficient (ADC) elevations. Their WM proportion was significantly decreased (p = 0.003) as was the WM proportion in the frontal region (p = 0.007). (1)H MRS showed no significant abnormalities. The findings of WM abnormalities and decreased optic radiation and middle cerebellar peduncle FA in the FD study group, suggest compromised myelination and WM micro-structural integrity in FD brains. These neuroimaging results are consistent with clinical visual abnormalities and gait disturbance. Furthermore the frontal lobe atrophy is consistent with previously reported neuropsychological deficits.
authors.affiliation: Department of Pediatrics, New York University School of Medicine, 530 First Avenue, Suite 9Q, New York, NY 10016, USA. Felicia.Axelrod@nyumc.org
authors.forename: Felicia B
authors.initials: FB
authors.lastname: Axelrod
authors.forename: Max J
authors.initials: MJ
authors.lastname: Hilz
authors.forename: Dena
authors.initials: D
authors.lastname: Berlin
authors.forename: Po Lai
authors.initials: PL
authors.lastname: Yau
authors.forename: David
authors.initials: D
authors.lastname: Javier
authors.forename: Victoria
authors.initials: V
authors.lastname: Sweat
authors.forename: Hannah
authors.initials: H
authors.lastname: Bruehl
authors.forename: Antonio
authors.initials: A
authors.lastname: Convit
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004402:Dysautonomia, Familial / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D011522:Protons; D055815:Young Adult
chemical_list: D011522:Protons
references.citation: Clin Auton Res. 2001 Dec;11(6):343-9
references.pmid: 11794714
references.citation: J Comput Assist Tomogr. 1995 Jul-Aug;19(4):615-23
references.pmid: 7622696
references.citation: J Magn Reson B. 1996 Jun;111(3):209-19
references.pmid: 8661285
references.citation: Pediatrics. 1979 May;63(5):708-12
references.pmid: 440890
references.citation: Am J Hum Genet. 2001 Mar;68(3):598-605
references.pmid: 11179008
references.citation: J Neurol Sci. 1978 Nov;39(1):47-59
references.pmid: 731273
references.citation: Brain. 2008 Feb;131(Pt 2):559-72
references.pmid: 18083753
references.citation: Biol Psychiatry. 2004 Nov 1;56(9):613-9
references.pmid: 15522243
references.citation: Magn Reson Imaging. 2005 Oct;23(8):851-8
references.pmid: 16275423
references.citation: Lancet. 1962 Jun 9;1(7241):1216-8
references.pmid: 14450255
references.citation: Pediatrics. 1949 Apr;3(4):468-78
references.pmid: 18118947
references.citation: J Neurol Neurosurg Psychiatry. 1964 Apr;27:131-9
references.pmid: 14152534
references.citation: Physiol Rev. 2001 Apr;81(2):871-927
references.pmid: 11274346
references.citation: Hum Mol Genet. 2007 Sep 1;16(17):2097-104
references.pmid: 17591626
references.citation: AJR Am J Roentgenol. 1987 Aug;149(2):351-6
references.pmid: 3496763
references.citation: J Pediatr. 1955 Jun;46(6):663-70
references.pmid: 14368477
references.citation: Pediatrics. 1981 Apr;67(4):517-22
references.pmid: 7254974
references.citation: Acta Paediatr. 2006 Apr;95(4):457-62
references.pmid: 16720494
references.citation: J Neurosci Methods. 2005 Mar 15;142(1):67-76
references.pmid: 15652618
references.citation: Clin Auton Res. 2006 Apr;16(2):90-7
references.pmid: 16683067
references.citation: J Magn Reson Imaging. 2004 Jan;19(1):6-18
references.pmid: 14696215
references.citation: Psychiatry Res. 1999 Apr 26;90(2):113-23
references.pmid: 10482383
references.citation: Arch Neurol. 1964 May;10:459-63
references.pmid: 14120637
references.citation: Neuroimage. 2001 Jul;14(1 Pt 1):21-36
references.pmid: 11525331
references.citation: Neurology. 1965 Apr;15:321-7
references.pmid: 14280594
references.citation: Eur J Radiol. 1999 May;30(2):125-31
references.pmid: 10401593
references.citation: Ann N Y Acad Sci. 1974 Mar 22;228(0):288-300
references.pmid: 4526282
references.citation: Magn Reson Med. 1998 Jun;39(6):928-34
references.pmid: 9621916