Nerve ultrasound characterizes AMN polyneuropathy as inhomogeneous and focal hypertrophic

Abstract

Objective: High-resolution nerve ultrasound (HRUS) is a painless tool to quickly evaluate peripheral nerve morphology in vivo. This study set out to characterize peripheral nerve involvement in X-linked adrenomyeloneuropathy (AMN) by HRUS.

Methods: Thirteen adults with genetically proven AMN were examined using the Ultrasound pattern sum score (UPSS) to evaluate morphological abnormalities of peripheral nerves, vagal nerves, as well as cervical nerve roots. Ultrasound results were correlated with clinical findings and nerve conduction studies.

Results: UPSS was increased in six out of 13 patients. Nerve enlargement was mostly inhomogeneous and regional. The median, ulnar, and vagal nerves presented with more prominent alterations than nerves of the lower limbs. The proximal-to-distal ratio was significantly enlarged for the median nerve. HRUS findings matched nerve conduction studies, but identified one patient with enlarged nerves and yet normal conduction velocities. Sonographic findings did not correlate with disease duration or disease severity as assessed by the spastic paraplegia rating scale.

Conclusion: HRUS reveals significant multifocal regional nerve swellings with reduced echo intensity as the morphological equivalent of electrophysiological peripheral nerve affection in AMN patients. Ultrasound and NCS characteristics in AMN seem to differ from other demyelinating neuropathies like CIDP or CMT1a.

Trial registration: German clinical-trial-register (DRKS) ( DRKS-ID 00005253 ) Registered 15 October 2013.

Keywords: Adrenoleukodystrophy; Adrenomyeloneuropathy; High resolution nerve ultrasound; Nerve conduction study; Peripheral neuropathy; Ultrasound pattern sum score; Very long chain fatty acids; X-ALD.

Fig. 1

Representative ultrasound images of the median nerve (MN) in different diseases / disease states are shown per row. The left column (pictures labeled with an (a)) depicts cross sections of the upper arm (UA) and in the right column (b) cross sections of the forearm (FA). All ultrasound cross sections were recorded according to the UPSS protocol as previously described [8, 9]. All ultrasound pictures are presented at the same resolution and are therefore comparable in size (scale bar indicates 0.5 cm). In the first row (Ia&b) the inhomogenously enlarged median nerve of a patient with AMN and demyelinating polyneuropathy is seen (Class 1 according to [11]), with a cross-sectional area (CSA) of 44 mm² in the UA (Ia) and 11mm² in the FA – (Ib). Images of an AMN patient without neuropathy (Class 3, pictures IIa&b) are presented in the second row. The CSA of the MN was 8mm² in the UA (IIa) and 9mm² in the FA (IIb). CSA values of AMN patients without electrophysiologically proven peripheral neuropathy (PNP) correspond to normal values of healthy controls as published before [8]. For comparison purposes, we added representative pictures of a chronic inflammatory demyelinating polyneuropathy (CIDP) patient (Class 2) in the thirds row (IIIa & b) and of a Charcot-Marie-Tooth type 1a (CMT1a) patient (IVa & b) in the fourth row. The CIDP patient shows an inhomogeneously enlarged median nerve (78mm² in the UA (IIIa) and 13mm² in the FA (IIIb)) which is hyperechoic due to more perifascicular tissue. Nerve segments of the median nerve of a CMT1a patient (IVa & b) are in contrast homogeneously enlarged with 44mm² in the UA (IVa) and 30mm² in the FA (IVb) without significant changes in echointensity. The CSA in CMT1a equals the 3-4fold of known normal values in healthy adults

Fig. 2

(a) Scatter plot showing an inverse correlation of motor conduction velocity (CV) of tibial and ulnar nerves with the cross-sectional area (CSA) of the corresponding nerves. In addition, CVs correlate inversely with the ultrasound pattern sum score (UPSS): the higher the UPSS (indicating overall nerve enlargement), the lower the CV. (b) Receiver Operating Characteristic (ROC) curve analysis for the ultrasound pattern sum score (UPSS) (summarizing all enlarged nerve segments) to differentiate AMN with and without polyneuropathy: A score > 3 points is highly sensitive and specific for AMN with demyelinating neuropathy