Journal of Neurology

, Volume 256, Issue 8, pp 1307–1313 | Cite as

Striatal morphology correlates with sensory abnormalities in unaffected relatives of cervical dystonia patients

  • Richard A. Walsh
  • Robert Whelan
  • John O’Dwyer
  • Sean O’Riordan
  • Siobhan Hutchinson
  • Risteard O’Laoide
  • Kevin Malone
  • Richard Reilly
  • Michael Hutchinson
Original Communication

Abstract

Structural grey matter abnormalities have been described in adult-onset primary torsion dystonia (AOPTD). Altered spatial discrimination thresholds are found in familial and sporadic AOPTD and in some unaffected relatives who may be non-manifesting gene carriers. Our hypothesis was that a subset of unaffected relatives with abnormal spatial acuity would have associated structural abnormalities. Twenty-eight unaffected relatives of patients with familial cervical dystonia, 24 relatives of patients with sporadic cervical dystonia and 27 control subjects were recruited. Spatial discrimination thresholds (SDTs) were determined using a grating orientation task. High-resolution magnetic resonance imaging (MRI) images (1.5 T) were analysed using voxel-based morphometry. Unaffected familial relatives with abnormal SDTs had reduced caudate grey matter volume (GMV) bilaterally relative to those with normal SDTs (right Z = 3.45, left Z = 3.81), where there was a negative correlation between SDTs and GMV (r = −0.76, r 2 = 0.58, p < 0.0001). Familial relatives also had bilateral sensory cortical expansion relative to unrelated controls (right Z = 4.02, left Z = 3.79). Unaffected relatives of patients with sporadic cervical dystonia who had abnormal SDTs had reduced putaminal GMV bilaterally compared with those with normal SDTs (right Z = 3.96, left Z = 3.45). Sensory abnormalities in some unaffected relatives correlate with a striatal substrate and may be a marker of genetic susceptibility in these individuals. Further investigation of grey matter changes as a candidate endophenotype may assist future genetic studies of dystonia.

Keywords

Dystonia Voxel-based morphometry Spatial discrimination Basal ganglia 

Notes

Acknowledgements

This study was funded by Dystonia Ireland and a University College Dublin Seed Funding grant.

Conflict of interest statement

The authors report no conflicts of interest.

References

  1. 1.
    Waddy HM, Fletcher NA, Harding AE, Marsden CD (1991) A genetic study of idiopathic focal dystonias. Ann Neurol 29:320–324. doi: 10.1002/ana.410290315 PubMedCrossRefGoogle Scholar
  2. 2.
    Jarman PR, del Grosso N, Valente EM, Leube B, Cassetta E, Bentivoglio AR, Waddy HM, Uitti RJ, Maraganore DM, Albanese A, Frontali M, Auburger G, Bressman SB, Wood NW, Nygaard TG (1999) Primary torsion dystonia: the search for genes is not over. J Neurol Neurosurg Psychiatry 67:395–397. doi: 10.1136/jnnp.67.3.395 PubMedCrossRefGoogle Scholar
  3. 3.
    Tinazzi M, Rosso T, Fiaschi A (2003) Role of the somatosensory system in primary dystonia. Mov Disord 18:605–622. doi: 10.1002/mds.10398 PubMedCrossRefGoogle Scholar
  4. 4.
    Frima N, Nasir J, Grunewald R (2008) Abnormal vibration-induced illusion of movement in idiopathic focal dystonia: an endophenotypic marker? Mov Disord 23:373–377. doi: 10.1002/mds.21838 PubMedCrossRefGoogle Scholar
  5. 5.
    Meunier S, Hallett M (2005) Endophenotyping: a window to the pathophysiology of dystonia. Neurology 65:792–793. doi: 10.1212/01.wnl.0000177919.02950.4a PubMedCrossRefGoogle Scholar
  6. 6.
    O’Dwyer JP, O’Riordan S, Saunders-Pullman R, Bressman SB, Molloy F, Lynch T, Hutchinson M (2005) Sensory abnormalities in unaffected relatives in familial adult-onset dystonia. Neurology 65:938–940. doi: 10.1212/01.wnl.0000176068.23983.a8 PubMedCrossRefGoogle Scholar
  7. 7.
    Walsh R, O’Dwyer JP, Sheikh I, O’Riordan S, Lynch T, Hutchinson M (2007) Sporadic adult onset dystonia: sensory abnormalities as an endophenotype in unaffected relatives. J Neurol Neurosurg Psychiatry 78:980–983. doi: 10.1136/jnnp.2006.105585 PubMedCrossRefGoogle Scholar
  8. 8.
    Garraux G, Bauer A, Hanakawa T, Wu T, Kansaku K, Hallett M (2004) Changes in brain anatomy in focal hand dystonia. Ann Neurol 55:736–739. doi: 10.1002/ana.20113 PubMedCrossRefGoogle Scholar
  9. 9.
    Black KJ, Ongur D, Perlmutter JS (1998) Putamen volume in idiopathic focal dystonia. Neurology 51:819–824PubMedGoogle Scholar
  10. 10.
    Colosimo C, Pantano P, Calistri V, Totaro P, Fabbrini G, Berardelli A (2005) Diffusion tensor imaging in primary cervical dystonia. J Neurol Neurosurg Psychiatry 76:1591–1593. doi: 10.1136/jnnp.2004.056614 PubMedCrossRefGoogle Scholar
  11. 11.
    Etgen T, Muhlau M, Gaser C, Sander D (2006) Bilateral putaminal grey-matter increase in primary blepharospasm. J Neurol Neurosurg Psychiatry 77:1017–1020. doi: 10.1136/jnnp.2005.087148 PubMedCrossRefGoogle Scholar
  12. 12.
    Bressman SB, de Leon D, Brin MF, Greene PE, Fahn S, Breakefield XO, Risch NJ (1989) Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance. Ann Neurol 26:612–620. doi: 10.1002/ana.410260505 PubMedCrossRefGoogle Scholar
  13. 13.
    Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26:839–851. doi: 10.1016/j.neuroimage.2005.02.018 PubMedCrossRefGoogle Scholar
  14. 14.
    Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19:1233–1239. doi: 10.1016/S1053-8119(03)00169-1 PubMedCrossRefGoogle Scholar
  15. 15.
    Genovese CR, Lazar NA, Nichols T (2002) Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15:870–878. doi: 10.1006/nimg.2001.1037 PubMedCrossRefGoogle Scholar
  16. 16.
    Fox PT, Laird AR, Fox SP, Fox PM, Uecker AM, Crank M, Koenig SF, Lancaster JL (2005) BrainMap taxonomy of experimental design: description and evaluation. Hum Brain Mapp 25:185–198. doi: 10.1002/hbm.20141 PubMedCrossRefGoogle Scholar
  17. 17.
    Obermann M, Yaldizli O, De Greiff A, Lachenmayer ML, Buhl AR, Tumczak F, Gizewski ER, Diener HC, Maschke M (2007) Morphometric changes of sensorimotor structures in focal dystonia. Mov Disord 22:1117–1123. doi: 10.1002/mds.21495 PubMedCrossRefGoogle Scholar
  18. 18.
    Delmaire C, Vidailhet M, Elbaz A, Bourdain F, Bleton J-P, Sangla S, Meunier S, Terrier A, Lehéricy S (2007) Structural abnormalities in the cerebellum and sensorimotor circuit in writer’s cramp. Neurology 69:376–380. doi: 10.1212/01.wnl.0000266591.49624.1a PubMedCrossRefGoogle Scholar
  19. 19.
    Moore CE, Schady W (2000) Investigation of the functional correlates of reorganization within the human somatosensory cortex. Brain 123:1883–1895. doi: 10.1093/brain/123.9.1883 PubMedCrossRefGoogle Scholar
  20. 20.
    Brown LL, Schneider JS, Lidsky TI (1997) Sensory and cognitive functions of the basal ganglia. Curr Opin Neurobiol 7:157–163. doi: 10.1016/S0959-4388(97)80003-7 PubMedCrossRefGoogle Scholar
  21. 21.
    Peller M, Zeuner KE, Munchau A, Quatarone A, Weiss M, Knutzen A, Hallett M, Deuschl G, Siebner HR (2006) The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer’s cramp. Brain 129:2697–2708. doi: 10.1093/brain/awl181 PubMedCrossRefGoogle Scholar
  22. 22.
    Sathian K, Zangaladze A, Green J, Vitek JL, DeLong MR (1997) Tactile spatial acuity and roughness discrimination: impairments due to aging and Parkinson’s disease. Neurology 49:168–177PubMedGoogle Scholar
  23. 23.
    Murase N, Kaji R, Shimazu H, Katayama-Hirpta M, Ikeda A, Kohara N, Kimura J, Shibasaki H, Rothwell JC (2000) Abnormal premovement gating of somatosensory input in writer’s cramp. Brain 123:1813–1829. doi: 10.1093/brain/123.9.1813 PubMedCrossRefGoogle Scholar
  24. 24.
    Carbon M, Su S, Dhawan V, Raymond D, Bressman S, Eidelberg D (2004) Regional metabolism in primary torsion dystonia: effects of penetrance and genotype. Neurology 62:1384–1390PubMedGoogle Scholar
  25. 25.
    Edwards MJ, Huang YZ, Wood NW, Rothwell JC, Bhatia KP (2003) Different patterns of electrophysiological deficits in manifesting and non-manifesting carriers of the DYT1 mutation. Brain 126:2074–2080. doi: 10.1093/brain/awg209 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Richard A. Walsh
    • 1
  • Robert Whelan
    • 1
    • 3
    • 4
  • John O’Dwyer
    • 1
  • Sean O’Riordan
    • 1
  • Siobhan Hutchinson
    • 1
  • Risteard O’Laoide
    • 2
  • Kevin Malone
    • 3
  • Richard Reilly
    • 4
  • Michael Hutchinson
    • 1
  1. 1.Department of NeurologySt. Vincent’s University HospitalDublin 4Ireland
  2. 2.Department of RadiologySt. Vincent’s University HospitalDublinIreland
  3. 3.Department of PsychiatrySt. Vincent’s University HospitalDublinIreland
  4. 4.Department of Electronic EngineeringUniversity College DublinDublinIreland

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