title: Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia.
abstract: Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values < 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia type 3. Within the cerebellar nuclei, reductions were significant when comparing spinocerebellar ataxia type 6 and Friedreich's ataxia to matched controls (P < 0.01, bootstrap-corrected cluster-size threshold; two-sample t-tests). Susceptibility weighted imaging allowed depiction of atrophy of the cerebellar nuclei in patients with Friedreich's ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia type 6, pathology was not restricted to the cerebellar cortex but also involved the cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand, revealed that pathology in Friedreich's ataxia and spinocerebellar ataxia type 3 is not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar cortex despite no or little structural changes.
authors.affiliation: 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany stefanescu.m.roxana@gmail.com.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Stefanescu
authors.affiliation: 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Dohnalek
authors.affiliation: 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Maderwald
authors.affiliation: 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Thürling
authors.affiliation: 3 Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany 4 Department of Neurology, University of Bonn, Bonn, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Minnerop
authors.affiliation: 5 Department of Computer Sciences, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beck
authors.affiliation: 6 Department of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schlamann
authors.affiliation: 7 Institute of Cognitive Neuroscience, University College London, London, UK.
authors.forename: Joern
authors.initials: J
authors.lastname: Diedrichsen
authors.affiliation: 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany 6 Department of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Essen, Germany 8 Division of Medical Physics in Radiology, University of Heidelberg and German Cancer Research Centre, Heidelberg, Germany.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ladd
authors.affiliation: 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Timmann
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D002525:Cerebellar Cortex / Q000473:pathology*; D002529:Cerebellar Nuclei / Q000473:pathology*; D005260:Female; D005621:Friedreich Ataxia / Q000473:pathology*; D006801:Humans; D017827:Machado-Joseph Disease / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020754:Spinocerebellar Ataxias / Q000473:pathology*; D013132:Spinocerebellar Degenerations / Q000473:pathology
keywords: cerebellar atrophy; dentate nuclei; functional magnetic resonance imaging; hereditary ataxia; spinocerebellar degeneration; structural magnetic resonance imaging
references.citation: Exp Brain Res. 1987;66(3):577-88
references.pmid: 3609202
references.citation: Brain. 1996 Oct;119 ( Pt 5):1497-505
references.pmid: 8931575
references.citation: MAGMA. 2008 Mar;21(1-2):63-72
references.pmid: 18064501
references.citation: Neuroimage. 1995 Jun;2(2):157-65
references.pmid: 9343598
references.citation: Hum Brain Mapp. 2012 Nov;33(11):2741-9
references.pmid: 21938757
references.citation: Cerebellum. 2010 Mar;9(1):22-8
references.pmid: 19513801
references.citation: Acta Neuropathol. 1998 Feb;95(2):199-204
references.pmid: 9498057
references.citation: Brain Lang. 2004 May;89(2):362-9
references.pmid: 15068919
references.citation: Neuroimage. 2011 Aug 1;57(3):1184-91
references.pmid: 21640191
references.citation: Neurosci Lett. 2006 Nov 20;408(3):230-5
references.pmid: 17005321
references.citation: Nat Rev Neurol. 2009 Apr;5(4):222-34
references.pmid: 19347027
references.citation: Clin Neurophysiol. 2008 Nov;119(11):2528-37
references.pmid: 18835217
references.citation: Ann Neurol. 1999 Jul;46(1):123-5
references.pmid: 10401790
references.citation: Acta Neuropathol. 2007 Aug;114(2):163-73
references.pmid: 17443334
references.citation: Ann Neurol. 1996 Apr;39(4):490-9
references.pmid: 8619527
references.citation: J Clin Neurosci. 2010 Jun;17(6):751-5
references.pmid: 20359894
references.citation: Brain. 2013 Mar;136(Pt 3):905-17
references.pmid: 23423669
references.citation: Acta Neuropathol. 2000 Oct;100(4):371-6
references.pmid: 10985694
references.citation: Curr Opin Neurol. 2011 Aug;24(4):339-45
references.pmid: 21734495
references.citation: Nature. 1996 Aug 29;382(6594):805-7
references.pmid: 8752272
references.citation: Hum Brain Mapp. 2001 Jun;13(2):55-73
references.pmid: 11346886
references.citation: Hum Brain Mapp. 2012 Aug;33(8):1780-91
references.pmid: 21674694
references.citation: J Neurol. 2010 Aug;257(8):1406-8
references.pmid: 20354716
references.citation: Cerebellum. 2012 Jun;11(2):384-91
references.pmid: 20596807
references.citation: Neuroimage. 2011 Apr 15;55(4):1633-44
references.pmid: 21224001
references.citation: Neuroimage. 2006 Oct 15;33(1):127-38
references.pmid: 16904911
references.citation: Eur J Neurol. 2014 Apr;21(4):552-62
references.pmid: 24418350
references.citation: Cerebellum. 2012 Sep;11(3):749-60
references.pmid: 22198871
references.citation: Neuroimage. 2003 Dec;20(4):2343-56
references.pmid: 14683734
references.citation: Neuroimage. 2007 Oct 15;38(1):95-113
references.pmid: 17761438
references.citation: Neuropsychologia. 1971 Mar;9(1):97-113
references.pmid: 5146491
references.citation: J Neurophysiol. 2004 Feb;91(2):1102-7
references.pmid: 14534284
references.citation: Eur J Neurol. 2014 Aug;21(8):1131-1136
references.pmid: 24779923
references.citation: J Neurol. 2012 Dec;259(12):2673-80
references.pmid: 22711160
references.citation: Mol Neurobiol. 2014 Jun;49(3):1513-31
references.pmid: 24293103
references.citation: Neurodegener Dis. 2011;8(6):470-5
references.pmid: 21659723
references.citation: Neuroimage. 2009 May 15;46(1):39-46
references.pmid: 19457380
references.citation: Lancet Neurol. 2010 Sep;9(9):885-94
references.pmid: 20723845
references.citation: Cerebellum. 2013 Aug;12(4):493-503
references.pmid: 23389921
references.citation: Neuroimage. 2012 Aug 15;62(2):1040-50
references.pmid: 22261372
references.citation: J Neurol Neurosurg Psychiatry. 1994 Jan;57(1):51-7
references.pmid: 8301305
references.citation: Neuroimage. 2009 May 1;45(4):1162-72
references.pmid: 19349231
references.citation: Prog Neurobiol. 2013 May;104:38-66
references.pmid: 23438480
references.citation: Neurology. 2006 Jun 13;66(11):1717-20
references.pmid: 16769946
references.citation: J Cell Biol. 2012 Apr 16;197(2):167-77
references.pmid: 22508507
references.citation: Neuroimage. 2005 May 1;25(4):1325-35
references.pmid: 15850749
references.citation: Neuroimage. 2013 Jan 15;65:299-314
references.pmid: 23036448
references.citation: Neuroimage. 2012 Sep;62(3):1593-9
references.pmid: 22634862
references.citation: Insights Imaging. 2011 Jun;2(3):335-347
references.pmid: 22347957
references.citation: Magn Reson Med. 2000 Jul;44(1):162-7
references.pmid: 10893535
references.citation: Eur J Neurosci. 2010 Apr;31(8):1402-13
references.pmid: 20384784
references.citation: Neuropathol Appl Neurobiol. 2009 Oct;35(5):515-27
references.pmid: 19207264
references.citation: Brain. 1991 Aug;114 ( Pt 4):1559-73
references.pmid: 1884166
references.citation: Exp Brain Res. 2013 Jul;228(2):243-54
references.pmid: 23732948
references.citation: J Mol Med (Berl). 2010 Apr;88(4):323-9
references.pmid: 19997898
references.citation: J Neuropathol Exp Neurol. 2013 Feb;72(2):78-90
references.pmid: 23334592
references.citation: Neuroimage. 2011 Feb 14;54(4):2612-22
references.pmid: 21081171
references.citation: Blood. 2007 Jul 1;110(1):401-8
references.pmid: 17379741
references.citation: Neuroimage Clin. 2014 Aug 23;6:93-9
references.pmid: 25379420
references.citation: Neuroimage. 2012 Nov 15;63(3):1421-31
references.pmid: 22892334
references.citation: Brain Res. 2012 Aug 30;1471:138-54
references.pmid: 22771856
references.citation: Magn Reson Imaging. 2009 Oct;27(8):1163-74
references.pmid: 19249168
references.citation: Neuroimage. 2010 Jan 1;49(1):158-68
references.pmid: 19631275
references.citation: Neuroimage. 2011 Feb 1;54(3):1786-94
references.pmid: 20965257
references.citation: Cerebellum. 2008;7(4):589-94
references.pmid: 19002543
references.citation: Brain. 1998 Sep;121 ( Pt 9):1687-93
references.pmid: 9762957
references.citation: J Comp Neurol. 1994 May 1;343(1):183-92
references.pmid: 8027435
references.citation: Neuroimage. 1999 Sep;10(3 Pt 1):233-60
references.pmid: 10458940
references.citation: Cerebellum. 2005;4(1):62-73
references.pmid: 15895563
references.citation: Acta Neuropathol. 2012 Jul;124(1):1-21
references.pmid: 22684686