Advertisement

Journal of Neurology

, Volume 255, Issue 12, pp 1904–1909 | Cite as

Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2

  • Martina MinneropEmail author
  • Eileen Luders
  • Karsten Specht
  • Jürgen Ruhlmann
  • Christiane Schneider-Gold
  • Rolf Schröder
  • Paul M. Thompson
  • Arthur W. Toga
  • Thomas Klockgether
  • Cornelia Kornblum
ORIGINAL COMMUNICATION

Abstract

Myotonic dystrophy type 2 (DM2) is an autosomal dominantly inherited multisystemic disorder and a common cause of muscular dystrophy in adults. Although neuromuscular symptoms predominate, there is clinical and imaging evidence of cerebral involvement. We used voxel-based morphometry (VBM) based on T1-weighted magnetic resonance images to investigate brain morphology in 13 DM2 patients in comparison to 13 sex- and age-matched controls. Further, we employed novel computational surface-based methods that specifically assess callosal thickness. We found grey and white matter loss along cerebral midline structures in our patient group. Grey matter reductions were present in brainstem and adjacent hypothalamic and thalamic regions, while white matter was mainly reduced in corpus callosum. The reduced callosal size was highly significant and independently confirmed by different methods. Our data provide first evidence for grey and white matter loss along brain midline structures in DM2 patients. The reduced size of the corpus callosum further extends the spectrum of white matter changes in DM2 and may represent the morphological substrate of neuropsychological abnormalities previously described in this disorder.

Key words

DM2 brainstem corpus callosum VBM morphometry 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Antonini G, Mainero C, Romano A,Giubilei F, Ceschin V, Gragnani F,Morino S, Fiorelli M, Soscia F, DiPasquale A, Caramia F (2004) Cerebralatrophy in myotonic dystrophy: a voxelbased morphometric study. J NeurolNeurosurg Psychiatry 75:1611–1613CrossRefGoogle Scholar
  2. 2.
    Ashburner J, Friston KJ (2000) Voxel-basedmorphometry – the methods.Neuroimage 11:805–821PubMedCrossRefGoogle Scholar
  3. 3.
    Ciafaloni E, Mignot E, Sansone V,Hilbert JE, Lin L, Lin X, Liu LC, PigeonWR, Perlis ML, Thornton CA (2008)The hypocretin neurotransmissionsystem in myotonic dystrophy type 1.Neurology 70:226–230PubMedCrossRefGoogle Scholar
  4. 4.
    Evangelou N, Konz D, Esiri MM, SmithS, Palace J, Matthews PM (2000)Regional axonal loss in the corpuscallosum correlates with cerebral whitematter lesion volume and distributionin multiple sclerosis. Brain 123:1845–1849PubMedCrossRefGoogle Scholar
  5. 5.
    Giubilei F, Antonini G, Bastianello S,Morino S, Paolillo A, Fiorelli M,Ferretti C, Fieschi C (1999) Excessivedaytime sleepiness in myotonicdystrophy. J Neurol Sci 164:60–63PubMedCrossRefGoogle Scholar
  6. 6.
    Good CD, Johnsrude IS, Ashburner J,Henson N, Friston KJ, Frackowiak RS(2001) A voxel-based morphometricstudy of ageing in 465 normal adulthuman brains. Neuroimage 14:21–36PubMedCrossRefGoogle Scholar
  7. 7.
    Good CD, Johnsrude I, Ashburner J,Henson RN, Friston KJ, Frackowiak RS(2001) Cerebral asymmetry and theeffects of sex and handedness on brainstructure: a voxel-based morphometricanalysis of 465 normal adult humanbrains. Neuroimage 14:685–700PubMedCrossRefGoogle Scholar
  8. 8.
    Hashimoto T, Taxama M, Miyazaki M,Miyazaki M, Murakawa K, Kawai H,Nishitani H, Kuroda Y (1995) Neuroimagingstudy of myotonic dystrophy.I. Magnetic resonance imaging of thebrain. Brain Dev 17:24–27PubMedCrossRefGoogle Scholar
  9. 9.
    Hund E, Jansen O, Koch MC, Ricker K,Fogel W, Niedermaier N, Otto M, KuhnE, Meinck HM (1997) Proximal myotonicmyopathy with MRI white matterabnormalities of the brain. Neurology48:33–37PubMedGoogle Scholar
  10. 10.
    Kassubek J, Juengling FD, Hoffmann S,Rosenbohm A, Kurt A, Jurkat-Rott K,Steinbach P, Wolf M, Ludolph AC,Lehmann-Horn F, Lerche H, Weber YG(2003) Quantification of brain atrophyin patients with myotonic dystrophyand proximal myotonic myopathy: acontrolled 3-dimensional magneticresonance imaging study. NeurosciLett 348:73–76Google Scholar
  11. 11.
    Kornblum C, Reul J, Kress W, Grothe C,Amanatidis N, Klockgether T, SchroderR (2004) Cranial magnetic resonanceimaging in genetically proven myotonicdystrophy type 1 and 2. J Neurol251:710–714PubMedCrossRefGoogle Scholar
  12. 12.
    Luders E, Narr KL, Zaidel E, ThompsonPM, Jancke L, Toga AW (2006) Parasagittalasymmetries of the corpus callosum.Cereb Cortex 16:346–354PubMedCrossRefGoogle Scholar
  13. 13.
    Luders E, Rex DE, Narr KL, Woods RP,Jancke L, Thompson PM, Mazziotta JC,Toga AW (2003) Relationships betweensulcal asymmetries and corpus callosumsize: gender and handednesseffects. Cereb Cortex 13:1084–1093PubMedCrossRefGoogle Scholar
  14. 14.
    Martinez-Rodriguez JE, Lin L, IranzoA, Genis D, Marti MJ, Santamaria J,Mignot E (2003) Decreased hypocretin-1 (Orexin-A) levels in the cerebrospinalfluid of patients with myotonicdystrophy and excessive daytimesleepiness. Sleep 26:287–290PubMedGoogle Scholar
  15. 15.
    Maurage CA, Udd B, Ruchoux MM,Vermersch P, Kalimo H, Krahe R,Delacourte A, Sergeant N (2005)Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease.Neurology 65:1636–1638PubMedCrossRefGoogle Scholar
  16. 16.
    Meola G, Sansone V, Perani D, ScaroneS, Cappa S, Dragoni C, Cattaneo E,Cotelli M, Gobbo C, Fazio F, SicilianoG, Mancuso M, Vitelli E, Zhang S,Krahe R, Moxley RT (2003) Executivedysfunction and avoidant personalitytrait in myotonic dystrophy type 1(DM-1) and in proximal myotonicmyopathy (PROMM/DM-2). NeuromusculDisord 13:813–821CrossRefGoogle Scholar
  17. 17.
    Meola G, Sansone V (2007) Cerebralinvolvement in myotonic dystrophies.Muscle Nerve 36:294–306PubMedCrossRefGoogle Scholar
  18. 18.
    Ota M, Sato N, Ohya Y Aoki Y,Mizukami, K, Mori T, Asada T (2006)Relationship between diffusion tensorimaging and brain morphology inpatients with myotonic dystrophy.Neurosci Lett 407:234–239PubMedCrossRefGoogle Scholar
  19. 19.
    Romeo V, Palmieri A, Squarzanti F,Ferrati C, Zucchetta P, Manara R,Trevisan C, Pegoraro E, Angelini C(2007) Brain involvement in myotonicdystrophy type 2. Neuromuscul Disord17(9–10):858CrossRefGoogle Scholar
  20. 20.
    Rudick RA, Fisher E, Lee JC, Simon J,Jacobs L (1999) Use of the brainparenchymal fraction to measurewhole brain atrophy in relapsingremittingMS. Multiple SclerosisCollaborative Research Group. Neurology53:1698–1704PubMedGoogle Scholar
  21. 21.
    Sansone V, Gandossini S, Cotelli M,Calabria M, Zanetti O, Meola G (2007)Cognitive impairment in adult myotonicdystrophies: a longitudinal study.Neurol Sci 28:9–15PubMedCrossRefGoogle Scholar
  22. 22.
    Sergeant N, Sablonniere B, Schraen-Maschke S, Ghestem A, Maurage CA,Wattez A, Vermersch P, Delacourte A(2001) Dysregulation of human brainmicrotubule-associated tau mRNAmaturation in myotonic dystrophytype 1. Hum Mol Genet 10:2143–2155PubMedCrossRefGoogle Scholar
  23. 23.
    Specht K, Minnerop M, Muller-Hubenthal J, Klockgether T (2005)Voxel-based analysis of multiplesystematrophy of cerebellar type:complementary results by combiningvoxel-based morphometry and voxel-basedrelaxometry. NeuroImage 25:287–293PubMedCrossRefGoogle Scholar
  24. 24.
    Vielhaber S, Jakubiczka S, Gaul C,Schoenfeld MA, Debska-Vielhaber G,Zierz S, Heinze HJ, Niessen HG,Kaufmann Jl (2006) Brain (1)H magneticresonance spectroscopic differencesin myotonic dystrophy type 2and type 1. Muscle Nerve 34:145–152PubMedCrossRefGoogle Scholar
  25. 25.
    Warwick MM, Doody GA, Lawrie SM,Kestelman JN, Best JJ, Johnstone EC(1999) Volumetric magnetic resonanceimaging study of the brain in subjectswith sex chromosome aneuploidies.J Neurol Neurosurg Psychiatry 66:628–632PubMedCrossRefGoogle Scholar
  26. 26.
    Westerhausen R, Kreuder F, Dos SantosSequeira S, Walter C, Woerner W,Wittling RA, Schweiger E, Wittling W(2006) The association of macro- andmicrostructure of the corpus callosumand language lateralisation. Brain Lang97:80–90PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • Martina Minnerop
    • 1
    • 2
    Email author
  • Eileen Luders
    • 3
  • Karsten Specht
    • 4
  • Jürgen Ruhlmann
    • 5
  • Christiane Schneider-Gold
    • 6
  • Rolf Schröder
    • 7
  • Paul M. Thompson
    • 3
  • Arthur W. Toga
    • 3
  • Thomas Klockgether
    • 1
  • Cornelia Kornblum
    • 1
  1. 1.Dept. of NeurologyUniversity Hospital of BonnBonnGermany
  2. 2.Brain Imaging Center West (BICW)JülichGermany
  3. 3.Laboratory of NeuroImaging, Dept. of NeurologyUCLA School of MedicineLos AngelesUSA
  4. 4.Dept. of Biological and Medical PsychologyUniversity of Bergen & Dept. of Medical Engineering, Haukeland University HospitalBergenNorway
  5. 5.Medical Center BonnBonnGermany
  6. 6.Dept. of NeurologyUniversity of GöttingenGöttingenGermany
  7. 7.Dept. of NeuropathologyUniversity of ErlangenErlangenGermany

Personalised recommendations