Journal of Neurology

, Volume 260, Issue 1, pp 268–274 | Cite as

Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with chenodeoxycholic acid

  • F. Ginanneschi
  • A. Mignarri
  • M. Mondelli
  • G. N. Gallus
  • M. Del Puppo
  • S. Giorgi
  • A. Federico
  • A. Rossi
  • M. T. Dotti
Original Communication

Abstract

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.

Keywords

Cerebrotendinous xanthomatosis Neurophysiology Neuropathy 

Notes

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.

References

  1. 1.
    Federico A, Dotti MT (1996) Cerebrotendinous xanthomatosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology. Elsevier, Amsterdam, pp 599–613Google Scholar
  2. 2.
    Kuritzky A, Berginer VM, Korczyn AD (1979) Peripheral neuropathy in cerebrotendinous xanthomatosis. Neurology 29:880–881PubMedCrossRefGoogle Scholar
  3. 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) 45:43–45CrossRefGoogle Scholar
  4. 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 PubMedCrossRefGoogle Scholar
  5. 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 PubMedCrossRefGoogle Scholar
  6. 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 PubMedCrossRefGoogle Scholar
  7. 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 PubMedCrossRefGoogle Scholar
  8. 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 49:469–475PubMedCrossRefGoogle Scholar
  9. 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 PubMedCrossRefGoogle Scholar
  10. 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 10:407–414PubMedCrossRefGoogle Scholar
  11. 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 PubMedCrossRefGoogle Scholar
  12. 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 PubMedCrossRefGoogle Scholar
  13. 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 PubMedCrossRefGoogle Scholar
  14. 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 PubMedCrossRefGoogle Scholar
  15. 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 PubMedCrossRefGoogle Scholar
  16. 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 112:139–146PubMedCrossRefGoogle Scholar
  17. 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 Google Scholar
  18. 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 PubMedCrossRefGoogle Scholar
  19. 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 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • F. Ginanneschi
    • 5
  • A. Mignarri
    • 1
  • M. Mondelli
    • 2
  • G. N. Gallus
    • 1
  • M. Del Puppo
    • 3
  • S. Giorgi
    • 4
  • A. Federico
    • 1
  • A. Rossi
    • 5
  • M. T. Dotti
    • 1
  1. 1.Neurometabolic Unit, Department of Neurological, Neurosurgical and Behavioural SciencesUniversity of SienaSienaItaly
  2. 2.Servizio di EMG, ASL 7SienaItaly
  3. 3.Department of Experimental Medicine, Medical SchoolUniversity of Milano-BicoccaMilanoItaly
  4. 4.Unit of Farmacy, AOUSSienaItaly
  5. 5.Section of Neurology and Clinical Neurophysiology, Department of Neurological, Neurosurgical and Behavioural SciencesUniversity of SienaSienaItaly

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