Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with chenodeoxycholic acid

• Published in: Journal of neurology Vol. 260; no. 1; pp. 268 - 274
• Main Authors: Ginanneschi, F., Mignarri, A., Mondelli, M., Gallus, G. N., Del Puppo, M., Giorgi, S., Federico, A., Rossi, A., Dotti, M. T.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 2013; Springer Nature B.V
• Subjects: Action Potentials - drug effects; Action Potentials - genetics; Adolescent; Adult; Aged; Axons; Chenodeoxycholic acid; Chenodeoxycholic Acid - therapeutic use; Cholestanetriol 26-Monooxygenase - genetics; Cholestanol - blood; Electrical stimuli; Electromyography; Female; Fibers; Genotypes; Humans; Logistic Models; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Myelin; Nerve conduction; Neural Conduction - drug effects; Neural Conduction - genetics; Neurologic Examination; Neurology; Neuroprotective Agents - therapeutic use; Neuroradiology; Neurosciences; Original Communication; Patients; Peripheral nerves; Phenotypes; Polyneuropathies - drug therapy; Polyneuropathies - etiology; Polyneuropathy; Statistics, Nonparametric; Xanthomatosis; Xanthomatosis, Cerebrotendinous - complications; Xanthomatosis, Cerebrotendinous - genetics; Young Adult; Cerebrotendinous xanthomatosis; Neuropathy; Neurophysiology
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-012-6630-3

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.