Nerve Ultrasound Detects Peripheral Nerve Enlargement in Cerebrotendinous Xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by variants in the CYP27A1 gene, resulting in cholestanol accumulation in various tissues, including peripheral nerves. Polyneuropathy is common but often under-recognized in CTX. This study aimed to evaluate the cross-sectional area (CSA) of peripheral nerves in CTX.

Six genetically confirmed CTX patients underwent clinical, electrophysiological, and ultrasonographic evaluations. Clinical severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and the Polyneuropathy Disability (PND) score. Nerve ultrasound was performed at standardized sites of the median, ulnar, tibial, and sural nerves, and at the supraclavicular brachial plexus. CSA values were compared with healthy controls.

Nerve conduction studies (NCS) identified demyelinating polyneuropathy in three patients. However, ultrasound showed nerve enlargement in all six, including those with normal NCS. The supraclavicular brachial plexus was enlarged in every patient. In 5 adult patients, enlargement was most consistently observed in the median nerve (4 at the wrist and forearm; 5 at the cubital fossa and upper arm), the ulnar nerve at the upper arm (5), and the fibular nerve at the fibular head (4).

This study demonstrates that nerve ultrasound can detect peripheral nerve enlargement in CTX, even in preclinical stages of polyneuropathy. Enlargement of peripheral nerves may be a sensitive marker of disease severity and peripheral nerve involvement. The role of nerve ultrasound as a diagnostic tool in CTX is promising, and future longitudinal studies are needed to determine its value in disease monitoring.