Journal of Neurology

, Volume 255, Issue 5, pp 738–744

The pulvinar sign: frequency and clinical correlations in Fabry disease

  • A. P. Burlina
  • R. Manara
  • C. Caillaud
  • J.-P. Laissy
  • M. Severino
  • I. Klein
  • A. Burlina
  • O. Lidove
ORIGINAL COMMUNICATION

Abstract

Fabry disease is an X-linked lysosomal deficiency of α-galactosidase A that results in cellular accumulation of galactoconjugates, mainly globotriaosylceramide, particularly in blood vessels. Neuroradiological findings include ischemic stroke, white matter lesions, vascular abnormalities (vertebrobasilar dolichoectasia and vessel tortuosity), and posterior thalamus involvement (the so called pulvinar sign). The purpose of our study was to investigate the presence of the increased pulvinar signal intensity on T1-weighted imaging – pulvinar sign and its relationship with other clinical findings, in a non-selected cohort of Fabry patients.

Methods

We performed a prospective analysis of two populations of patients (36 subjects) with Fabry disease. Patients were followed-up at the Department of Internal Medicine of the Bichat Hospital in Paris (France) and at the Neurological Clinic of the University Hospital of Padova (Italy). Brain MR studies of each patient included T1- and T2- weighted images, FLAIR sequences, and in some cases diffusion weighted images.

Results

A total of 36 patients (16 males, 20 females) were investigated in 14 families. The pulvinar sign was found in 5 male patients, but not in female patients. Seven patients had had at least one stroke (territorial or lacunar). There was no correlation between stroke and the pulvinar sign. All patients with the pulvinar sign had hypertrophic cardiomyopathy. Four patients out of five with the pulvinar sign were on dialysis or had a kidney transplantation.

Conclusions

Our findings suggest that the pulvinar sign is a highly specific sign of Fabry disease, found in male patients with cardiac signs and severe kidney involvement.

Key words

Fabry disease posterior thalamus pulvinar brain MRI T1 images 

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References

  1. 1.
    Desnick RJ, Ioannou YA, Eng CM (2001) α-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic & Molecular Bases of Inherited Disease, 8th ed, Vol 3. McGraw-Hill, New York, pp 3733−3774Google Scholar
  2. 2.
    MacDermot KD, Holmes A, Miners AH (2001) Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38:750−760PubMedCrossRefGoogle Scholar
  3. 3.
    MacDermot KD, Holmes A, Miners AH (2001) Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38:769−775PubMedCrossRefGoogle Scholar
  4. 4.
    Wang RY, Lelis A, Mirocha J, Wilcox WR (2007) Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med 9:34–45PubMedCrossRefGoogle Scholar
  5. 5.
    Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281:249−254PubMedCrossRefGoogle Scholar
  6. 6.
    Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H, et al. (2006) High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 79:31–40PubMedCrossRefGoogle Scholar
  7. 7.
    Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO (2001) Enzyme replacement therapy in Fabry disease. JAMA 285:2743–2749PubMedCrossRefGoogle Scholar
  8. 8.
    Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ; International Collaborative Fabry Disease Study Group (2001) Safety and efficacy of recombinant human α-galactosidase A replacement therapy in Fabry’s disease. N Engl J Med 345:9–16PubMedCrossRefGoogle Scholar
  9. 9.
    Fellgiebel A, Müller MJ, Ginsberg L (2006) CNS manifestations of Fabry’s disease. Lancet Neurol 5:791–795PubMedCrossRefGoogle Scholar
  10. 10.
    Ries M, Kim HJ, Zalewski CK, Mastroianni MA, Moore DF, Brady RO, Dambrosia JM, Schiffmann R, Brewer CC (2007) Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease. Brain 130:143–150PubMedCrossRefGoogle Scholar
  11. 11.
    Ginsberg L, Manara R, Valentine AR, Kendall B, Burlina AP (2006) Magnetic resonance imaging changes in Fabry disease. Acta Paediatrica 95(Suppl 451):57–62CrossRefGoogle Scholar
  12. 12.
    Lidove O, Klein I, Lelièvre JD, Lavallée P, Serfaty JM, Dupuis E, Papo T, Laissy JP (2006) Imaging features of Fabry disease. Am J Roentgenol 186:1184–1191CrossRefGoogle Scholar
  13. 13.
    Moore DF, Ye F, Schiffmann R, Butman JA (2003) Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic MR imaging sign of Fabry disease. Am J Neuroradiol 24:1096–1101PubMedGoogle Scholar
  14. 14.
    Takanashi JI, Barkovich AJ, Dillon WP, Sherr EH, Hart KA, Packman S (2003) T1 hyperintensity in the pulvinar: key imaging feature for the diagnosis of Fabry disease. Am J Neuroradiol 24:916–921PubMedGoogle Scholar
  15. 15.
    Fellgiebel A, Mazanek M, Whybra C, Beck M, Hartung R, Müller K-M, Scheurich A, Dellani PR, Stoeter P, Müller MJ (2006) Pattern of microstructural brain tissue alterations in Fabry disease: a diffusion-tensor imaging study. J Neurol 253:780–787PubMedCrossRefGoogle Scholar
  16. 16.
    Gavazzi C, Borsini W, Guerrini L, Della Nave R, Rocca MA, Tessa C, Büchner S, Belli G, Filippi M, Villari N, Mascalchi M (2006) Subcortical damage and cortical functional changes in men and women with Fabry disease: a multifaceted MR study. Radiology 241:492–500PubMedCrossRefGoogle Scholar
  17. 17.
    Manara R, Ginsberg L, Severino S, Valentine AR, Kendall B, Clarke JTR, Mehta A, Burlina AP (2007) White matter and pulvinar signal abnormalities in Fabry disease : data from the Fabry Outcome Survey (FOS). J Neurol 254(Suppl 3):III/13Google Scholar
  18. 18.
    Sahraian MA, Motamedi M, Azimi AR, Hasan Paknejad SM (2007) Bilateral pulvinar thalamic calcification in a patient with chronic cryptococcal meningitis. Eur J Neurol 14:e1–e2PubMedCrossRefGoogle Scholar
  19. 19.
    Schmahmann JD (2003) Vascular syndromes of the thalamus. Stroke 34:2264–2278PubMedCrossRefGoogle Scholar
  20. 20.
    Rolfs A (2006) Cryptogenic CVE due to Fabry disease: measuring its incidence. International Workshop on Lysosomal Storage Disorders. Budapest, communicationGoogle Scholar
  21. 21.
    Hegemann S, Hajioff D, Conti G, Beck M, Sunder-Plassmann G, Widmer U, Mehta A, Keilman A (2006) Hearing loss in Fabry disease: data from the Fabry Outcome Survey. Eur J Clin Invest 36:654–662PubMedCrossRefGoogle Scholar
  22. 22.
    Limberger A, Beck M, Delgado-Sanchez S, Keilman A (2007) Hearing loss in patients with Fabry disease. HNO 55:185–189PubMedCrossRefGoogle Scholar
  23. 23.
    Moore DF, Scott LTC, Gladwin MT, Altarescu G, Kaneski C, Suzuki K, Pease-Fye M, Ferri R, Brady RO, Herscovitch P, Schiffmann R (2001) Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 104:1506–1512PubMedCrossRefGoogle Scholar
  24. 24.
    Moore DF, Ye F, Brennan M-L, Gupta S, Barshop BA, Steiner RD, Rhead WJ, Brady RO, Hazen SL, Schiffmann R (2004) Ascorbate decreases Fabry cerebral hyperperfusion suggesting a reactive oxygen species abnormality: an arterial spin tagging study. J Magn Reson Imag 20:674–683CrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • A. P. Burlina
    • 1
  • R. Manara
    • 2
  • C. Caillaud
    • 3
  • J.-P. Laissy
    • 4
  • M. Severino
    • 2
  • I. Klein
    • 4
  • A. Burlina
    • 5
  • O. Lidove
    • 6
  1. 1.Dept. of Neuroscience, Neurological ClinicUniversity Hospital of PadovaItaly
  2. 2.Neuroradiology UnitUniversity Hospital of PadovaItaly
  3. 3.Dept. of GeneticsCochin HospitalParisFrance
  4. 4.Dept. of RadiologyBichat HospitalParisFrance
  5. 5.Dept. of Paediatrics Inherited Metabolic Diseases UnitUniversity Hospital of PadovaItaly
  6. 6.Service de Médecine InterneHôpital BichatParis Cedex 18France

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