European Radiology

, Volume 26, Issue 10, pp 3377–3382 | Cite as

Thickening of the cauda equina roots: a common finding in Krabbe disease

  • Misun Hwang
  • Giulio Zuccoli
  • Ashok Panigrahy
  • David Rodriguez
  • Michele D. Poe
  • Maria L. Escolar



Evaluation of Krabbe disease burden and eligibility for hematopoietic stem cell transplantation are often based on neuroimaging findings using the modified Loes scoring system, which encompasses central but not peripheral nervous system changes. We show that quantitative evaluation of thickened cauda equina nerve roots may improve the evaluation of Krabbe disease and therapeutic guidance.


Lumbar spine MRI scans of patients obtained between March 2013 and September 2013 were retrospectively evaluated and compared to those of controls. Quantitative evaluation of cauda equina roots was performed on the axial plane obtained approximately 5 mm below the conus medullaris. The largest nerves in the right and left anterior quadrants of the spinal canal were acquired.


Fifteen symptomatic patients with Krabbe disease (5–44 months old) and eleven age-matched controls were evaluated. The average areas (mm2) of anterior right and left nerves were 1.40 and 1.23, respectively, for patients and 0.61 and 0.60 for controls (differences: 0.79 and 0.63; p < 0.001).


Cauda equina nerve root thickening is associated with Krabbe disease in both treated and untreated patients. Adding lumbar spine MRI to the current neurodiagnostic protocols, which fails to account for peripheral nerve abnormalities, will likely facilitate the diagnosis of Krabbe disease.

Key Points

• Neuroimaging is valuable for evaluating cauda equina nerve abnormality in Krabbe disease

• MRI can be used to quantitatively evaluate cauda equina nerve thickening

• Lumbar MRI could be useful for diagnosis and treatment monitoring of Krabbe disease


Globoid cell leukodystrophy Cauda equina Spine Peripheral nervous system diseases Krabbe disease 



Chronic inflammatory demyelinating polyneuropathy




Globoid cell leukodystrophy


Metachromatic leukodystrophy



The scientific guarantor of this publication is Dr. Maria Escolar. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study has received funding by NIH/NINDS R01 NS061965-01, the DANA foundation, and The Legacy of Angels Foundation. Michele D Poe, PhD kindly provided statistical advice for this manuscript. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. This is a retrospective observational study performed at one institution.


  1. 1.
    Zlotogora J, Chakraborty S, Knowlton RG, Wenger DA (1990) Krabbe disease locus mapped to chromosome 14 by genetic linkage. Am J Hum Genet 47:37–44PubMedPubMedCentralGoogle Scholar
  2. 2.
    Suzuki K, Suzuki Y (1970) Globoid cell leucodystrophy (Krabbe’s disease): deficiency of galactocerebroside beta-galactosidase. Proc Natl Acad Sci U S A 66:302–309CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ida H, Kawame F, Kim SU, Eto Y (1990) Abnormality in cultured oligodendrocytes and Schwann cells isolated from the twitcher mouse. Mol Chem Neuropathol 13:195–204CrossRefPubMedGoogle Scholar
  4. 4.
    Warner T, Hammans S (2009) Practical Guide to Neurogenetics, 1st edn. Elsevier Health Sciences, PhiladelphiaGoogle Scholar
  5. 5.
    Wenger D, Suzuki K, Suzuki Y, Suzuk K (2001) The metabolic and molecular basis of inherited diseases, 9th edn. McGraw-Hill, New YorkGoogle Scholar
  6. 6.
    Harcourt B, Ashton N (1973) Ultrastructure of the optic nerve in Krabbe’s leucodystrophy. Br J Ophthalmol 57:885–891CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Brownstein S, Meagher-Villemure K, Polomeno RC, Little JM (1978) Optic nerve in globoid leukodystrophy (Krabbe’s disease). Ultrastructural changes. Arch Ophthalmol 96:864–870CrossRefPubMedGoogle Scholar
  8. 8.
    Barkovich A (2005) Pediatric neuroimaging, 4th edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  9. 9.
    Loes DJ, Peters C, Krivit W (1999) Globoid cell leukodystrophy: distinguishing early-onset from late-onset disease using a brain MR imaging scoring method. AJNR Am J of Neuroradiol 20:316–323Google Scholar
  10. 10.
    Lyon G, Hagberg B, Evrard P, Allaire C, Pavone L, Vanier M (1991) Symptomatology of late onset Krabbe’s leukodystrophy: the European experience. Dev Neurosci 13:240–244CrossRefPubMedGoogle Scholar
  11. 11.
    Marks HG, Scavina MT, Kolodny EH, Palmieri M, Childs J (1997) Krabbe’s disease presenting as a peripheral neuropathy. Muscle Nerve 20:1024–1028CrossRefPubMedGoogle Scholar
  12. 12.
    Shah S, Freeman E, Wolf V, Murthy S, Lotze T (2012) Intracranial optic nerve enlargement in infantile Krabbe disease. Neurology 78:e126CrossRefPubMedGoogle Scholar
  13. 13.
    Vasconcellos E, Smith M (1998) MRI nerve root enhancement in Krabbe disease. Pediatr Neurol 19:151–152CrossRefPubMedGoogle Scholar
  14. 14.
    Morana G, Biancheri R, Dirocco M et al (2009) Enhancing cranial nerves and cauda equina: an emerging magnetic resonance imaging pattern in metachromatic leukodystrophy and krabbe disease. Neuropediatrics 40:291–294CrossRefPubMedGoogle Scholar
  15. 15.
    Escolar ML, Poe MD, Provenzale JM et al (2005) Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. New Eng J Med 352:2069–2081CrossRefPubMedGoogle Scholar
  16. 16.
    Duffner PK, Caggana M, Orsini JJ et al (2009) Newborn screening for Krabbe disease: the New York State model. Pediatr Neurol 40:245–253CrossRefPubMedGoogle Scholar
  17. 17.
    Marks HG, Scavina MT, Kolodny EH, Palmieri M, Childs J (1997) Krabbe's disease presenting as a peripheral neuropathy. Muscle Nerve 20:1024–1028Google Scholar
  18. 18.
    Korn-Lubetzki I, Dor-Wollman T, Soffer D, Raas-Rothschild A, Hurvitz H, Nevo Y (2003) Early peripheral nervous system manifestations of infantile Krabbe disease. Pediatr Neurol 28:115–118CrossRefPubMedGoogle Scholar
  19. 19.
    Kale HA, Sklar E (2007) Magnetic resonance imaging findings in chronic inflammatory demyelinating polyneuropathy with intracranial findings and enhancing, thickened cranial and spinal nerves. Australas Radiol 51:B21–B24CrossRefPubMedGoogle Scholar
  20. 20.
    Haberlandt E, Scholl-Burgi S, Neuberger J et al (2009) Peripheral neuropathy as the sole initial finding in three children with infantile metachromatic leukodystrophy. Eur J Paediatr Neurol 13:257–260CrossRefPubMedGoogle Scholar
  21. 21.
    Webster HD (1962) Schwann cell alterations in metachromatic leukodystrophy: preliminary phase and electron microscopic observations. J Neuropathol Exp Neurol 21:534–554CrossRefPubMedGoogle Scholar
  22. 22.
    Bindu PS, Mahadevan A, Taly AB, Christopher R, Gayathri N, Shankar SK (2005) Peripheral neuropathy in metachromatic leucodystrophy. A study of 40 cases from south India. J Neurol Neurosurg Psychiatry 76:1698–1701CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Martinez AC, Ferrer MT, Fueyo E, Galdos L (1975) Peripheral neuropathy detected on electrophysiological study as first manifestation of metachromatic leucodystrophy in infancy. J Neurol Neurosurg Psychiatry 38:169–174CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Siddiqi ZA, Sanders DB, Massey JM (2006) Peripheral neuropathy in Krabbe disease. Neurology 67:268–272CrossRefPubMedGoogle Scholar
  25. 25.
    Ichioka T, Kishimoto Y, Brennan S, Santos GW, Yeager AM (1987) Hematopoietic cell transplantation in murine globoid cell leukodystrophy (the twitcher mouse): effects on levels of galactosylceramidase, psychosine, and galactocerebrosides. Proc Natl Acad Sci U S A 84:4259–4263CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Toyoshima E, Yeager AM, Brennan S, Santos GW, Moser HW, Mayer RF (1986) Nerve conduction studies in the Twitcher mouse (murine globoid cell leukodystrophy). J Neurol Sci 74:307–318CrossRefPubMedGoogle Scholar
  27. 27.
    Hofling AA, Kim JH, Fantz CR, Sands MS, Song SK (2009) Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy. NMR Biomed 22:1100–1106PubMedPubMedCentralGoogle Scholar
  28. 28.
    Morisaki S, Kawai Y, Umeda M et al (2011) In vivo assessment of peripheral nerve regeneration by diffusion tensor imaging. JMRI J Mag Res Imaging 33:535–542CrossRefGoogle Scholar
  29. 29.
    Cauley KA, Filippi CG (2013) Diffusion-tensor imaging of small nerve bundles: cranial nerves, peripheral nerves, distal spinal cord, and lumbar nerve roots--clinical applications. AJR Am J Roentgenol 201:W326–W335CrossRefPubMedGoogle Scholar
  30. 30.
    Escolar ML, Poe MD, Smith JK et al (2009) Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease. AJNR Am J Neuroradiol 30:1017–1021CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM (2005) Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology 236:221–230CrossRefPubMedGoogle Scholar
  32. 32.
    Given CA, Santos CC, Durden DD (2001) Intracranial and spinal MR imaging findings associated with Krabbe’s disease: case report. AJNR 22:1782–1785PubMedGoogle Scholar
  33. 33.
    Beslow LA, Schwartz ES, Bӧnneman CG (2008) Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease. Pediatr Radiol 38:694–696CrossRefPubMedGoogle Scholar
  34. 34.
    Ganesan K, Desai S, Hedge A (2010) Multiple cranial nerve enhancement: uncommon imaging finding in early infantile Krabbe’s disease. J Neuroimaging 20:195–197CrossRefPubMedGoogle Scholar
  35. 35.
    Bernal OG, Lenn N (2000) Multiple cranial nerve enhancement in early infantile Krabbe’s disease. Neurology 54:2348–2349CrossRefPubMedGoogle Scholar
  36. 36.
    Escolar ML, Poe MD, Martin HR, Kurtzberg J (2006) A staging system for infantile Krabbe disease to predict outcome after unrelated umbilical cord blood transplantation. Pediatrics 118(3):879–889CrossRefGoogle Scholar
  37. 37.
    Baumer P, Dombert T, Staub F et al (2011) Ulnar neuropathy at the elbow: MR neurography--nerve T2 signal increase and caliber. Radiology 260:199–206CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • Misun Hwang
    • 1
  • Giulio Zuccoli
    • 2
  • Ashok Panigrahy
    • 2
  • David Rodriguez
    • 1
  • Michele D. Poe
    • 3
  • Maria L. Escolar
    • 3
  1. 1.Department of Radiology of University of Pittsburgh Medical CenterPittsburghUSA
  2. 2.Section of Neuroradiology, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical CenterPittsburghUSA
  3. 3.Department of Pediatrics at Children’s Hospital of Pittsburgh of University of Pittsburgh Medical CenterPittsburghUSA

Personalised recommendations