Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with chenodeoxycholic acid

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.

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

“…It does, however, reduce abnormally elevated levels of cholestanol, apolipoprotein-B, apolipoprotein-A1, and albumin in the CSF and re-establishes the selective impermeability of the BBB . Improvements in neurophysiologic investigations: NCV and/or VEP (Ginanneschi et al 2013;Mondelli et al 1992;Mondelli et al 2001), EEG (Berginer et al 1984;van Heijst et al 1998), and bone mineral density (BMD) (Federico et al 1993;Martini et al 2013) have also been reported.…”

“…Abnormalities in patients with CTX have been reported for visual evoked potential (VEP), somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP), and nerve conduction velocity (NCV) studies, which may reflect delayed central conduction (Pilo-de-la-Fuente et al 2011;Tokimura et al 1992;Ginanneschi et al 2013). Electromyography (EMG)/NCV findings demonstrating motor or sensorimotor axonal neuropathy, demyelinating neuropathy, and mixed neuropathy have been reported (Pilo-de-laFuente et al 2011;Ginanneschi et al 2013;Verrips et al 2000b). Electron-dense deposits and crystal formation are a consistent histologic feature in liver biopsies from CTX patients.…”

Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous Xanthomatosis: A Case Report

“…In the literature, the primary pathological type of polyneuropathy in CTX is still a matter of debate. Altered lipid metabolism may cause a problem in myelin synthesis and the loss of myelin-axon integrity, leading to axonal degeneration [5]. Based on the nerve conduction study in our patient, the pathology was considered to be the sensory-motor demyelinating type.…”

“…A few previous reports have documented peripheral nervous system involvement in patients with CTX using a variety of measurement methods, including electrodiagnostic study, such as nerve conduction study and an electromyogram [3456], sural nerve biopsy [367], and muscle biopsy [6]. …”

“…Based on the electrodiagnostic study, polyneuropathy in CTX could be categorized as the motor axonal, sensory-motor axonal, motor demyelinating, or sensory-motor demyelinating type [456]. Some authors reported that the predominant pathology of polyneuropathy in CTX is demyelination [4]; whereas the other authors reported that the axonal type was predominant [56]. In the literature, the primary pathological type of polyneuropathy in CTX is still a matter of debate.…”