Skip to main content


Log in

Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with chenodeoxycholic acid

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript


Polyneuropathy has been reported in cerebrotendinous xanthomatosis (CTX), although its nature and possible association with certain genotypes and phenotypes are unclear. The effect of chronic administration of chenodeoxycholic acid (CDCA) on peripheral nerve conduction parameters is still debated. We report clinical, laboratory, and electrophysiological findings in 35 CTX patients. Twenty-six subjects (74.2 %) showed peripheral nerve abnormalities. Polyneuropathy was predominantly axonal (76.9 % of patients) and generally mild. No correlation was found between its presence and clinical or biochemical data. In polyneuropathic patients, CDCA treatment improved electrophysiological conduction parameters, irrespective of the duration of therapy. Improvement mainly concerned nerve conduction velocities, whereas most nerve amplitudes remained unchanged. This means that CDCA treatment did not influence the number of axons activated by maximum electrical stimulation but increased the conduction of the still-excitable fibers. Our findings may suggest that CDCA treatment promotes myelin synthesis in nerve fibers with residual unaffected axons. The effect of therapy may therefore depend largely on the extent of irreversible structural damage to axons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others


  1. Federico A, Dotti MT (1996) Cerebrotendinous xanthomatosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology. Elsevier, Amsterdam, pp 599–613

    Google Scholar 

  2. Kuritzky A, Berginer VM, Korczyn AD (1979) Peripheral neuropathy in cerebrotendinous xanthomatosis. Neurology 29:880–881

    Article  PubMed  CAS  Google Scholar 

  3. Ohnishi A, Yamashita Y, Goto I, Kuroiwa Y, Murakami S, Ikeda M (1979) De- and remyelination and onion bulb in cerebrotendinous xanthomatosis. Acta Neuropathol (Berl) 45:43–45

    Article  CAS  Google Scholar 

  4. Pop PH, Joosten E, van Spreeken A, Gabreëls-Festen A, Jaspar H, ter Laak H, Vos A (1984) Neuroaxonal pathology of central and peripheral nervous systems in cerebrotendinous xanthomatosis (CTX). Acta Neuropathol 64:259–264. doi:10.1007/BF00688117

    Article  PubMed  CAS  Google Scholar 

  5. Argov Z, Soffer D, Eisenberg S, Fujiyama J, Osame M (1986) Chronic demyelinating peripheral neuropathy in cerebrotendinous xanthomatosis. Ann Neurol 20:89–91. doi:10.1002/ana.410200115

    Article  PubMed  CAS  Google Scholar 

  6. Donaghy M, King RH, McKeran RO, Schwartz MS, Thomas PK (1990) Cerebrotendinous xanthomatosis: clinical, electrophysiological and nerve biopsy findings, and response to treatment with chenodeoxycholic acid. J Neurol 237:216–219. doi:10.1007/BF00314598

    Article  PubMed  CAS  Google Scholar 

  7. Tokimura Y, Kuriyama M, Arimura K, Fujiyama J, Osame M (1992) Electrophysiological studies in cerebrotendinous xanthomatosis. J Neurol Neurosurg Psychiatry 55:52–55. doi:10.1136/jnnp.55.1.52

    Article  PubMed  CAS  Google Scholar 

  8. Mondelli M, Rossi A, Scarpini C, Dotti MT, Federico A (1992) Evoked potentials in cerebrotendinous xanthomatosis and effect induced by chenodeoxycholic acid. Arch Neurol 49:469–475

    Article  PubMed  CAS  Google Scholar 

  9. Wang Z, Yuan Y, Zhang W, Zhang Y, Feng L (2007) Cerebrotendinous xanthomatosis with a compound heterozygote mutation and severe polyneuropathy. Neuropathology 27:62–66. doi:10.1111/j.1440-1789.2006.00739.x

    Article  PubMed  Google Scholar 

  10. Verrips A, van Engelen BG, ter Laak H, Gabreëls-Festen A, Janssen A, Zwarts M, Wevers RA, Gabreëls FJ (2000) Cerebrotendinous xanthomatosis. Controversies about nerve and muscle: observations in ten patients. Neuromuscul Disord 10:407–414

    Article  PubMed  CAS  Google Scholar 

  11. Chen SF, Tsai NW, Chang CC, Lu CH, Huang CR, Chuang YC, Chang WN (2011) Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis. BMC Neurol 11:63. doi:10.1186/1471-2377-11-63

    Article  PubMed  Google Scholar 

  12. Pilo B, de Blas G, Sobrido MJ, Navarro C, Grandas F, Barrero FJ, Moya MA, Jimenez-Escrig A (2011) Neurophysiological study in cerebrotendinous xanthomatosis. Muscle Nerve 43:531–536. doi:10.1002/mus.21905

    Article  PubMed  CAS  Google Scholar 

  13. Bromberg MB (2011) Review of the evolution of electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 43:780–794. doi:10.1002/mus.22038

    Article  PubMed  Google Scholar 

  14. De Stefano N, Dotti MT, Mortilla M, Federico A (2001) Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis. Brain 124:121–131. doi:10.1093/brain/124.1.121

    Article  PubMed  Google Scholar 

  15. Guerrera S, Stromillo ML, Mignarri A, Battaglini M, Marino S, Di Perri C, Federico A, Dotti MT, De Stefano N (2010) Clinical relevance of brain volume changes in patients with cerebrotendinous xanthomatosis. J Neurol Neurosurg Psychiatry 81:1189–1193. doi:10.1136/jnnp.2009.203364

    Article  PubMed  CAS  Google Scholar 

  16. Restuccia D, Di Lazzaro V, Servidei S, Colosimo C, Tonali P (1992) Somatosensory and motor evoked potentials in the assessment of cerebrotendinous xanthomatosis before and after treatment with chenodeoxycholic acid: a preliminary study. J Neurol Sci 112:139–146

    Article  PubMed  CAS  Google Scholar 

  17. Mondelli M, Sicurelli F, Scarpini C, Dotti MT, Federico A (2001) Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study. J Neurol Sci 190:29–33. doi:10.1016/S0022-510X(01)00563-9

    CAS  Google Scholar 

  18. Mignarri A, Rossi S, Ballerini M, lus GN, Del Puppo M, Galluzzi P, Federico A, Dotti MT (2011) Clinical relevance and neurophysiological correlates of spasticity in cerebrotendinous xanthomatosis. J Neurol 258:783–790. doi:10.1007/s00415-010-5829-4

    Article  PubMed  CAS  Google Scholar 

  19. van Heijst AF, Verrips A, Wevers RA, Cruysberg JR, Renier WO, Tolboom JJ (1998) Treatment and follow-up of children with cerebrotendinous xanthomatosis. Eur J Pediatr 157:313–316. doi:10.1007/s004310050818

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

All the authors exclude actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence work.

Ethical standard

This study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Author information

Authors and Affiliations


Corresponding author

Correspondence to M. T. Dotti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ginanneschi, F., Mignarri, A., Mondelli, M. et al. Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with chenodeoxycholic acid. J Neurol 260, 268–274 (2013).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: