Nerve ultrasound detects abnormally small nerves in patients with spinal and bulbar muscular atrophy

Abstract

Introduction/Aims: Sensory impairment secondary to dorsal root ganglion neuronopathy is common, although often subclinical, in X-linked spinal and bulbar muscular atrophy (SBMA).We investigated the hypothesis that nerves of SBMA patients show the same morphological changes on ultrasound as other inherited sensory neuronopathies and that these changes are distinct from those in axonal neuropathy. Methods:We compared the ultrasound cross-sectional areas (CSAs) of median, ulnar, sural, and tibial nerves of prospectively recruited SBMA patients with those of patients with acquired axonal neuropathy and healthy controls.We also compared the individual nerve CSAs of SBMA and neuropathy patients with our laboratory reference values.Results: There were 7 SBMA patients, 18 neuropathy patients, and 42 healthy controls.The nerve CSAs of the SBMA patients were significantly smaller than those of patients in the other two groups. The changes were most prominent in the upper limbs (p < .001), with the nerves of the SBMA patients being on average approximately half the size of the controls and a third the size of the neuropathy patients.On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one SBMA patient.Discussion: These ultrasound changes are similar to those reported in other inherited sensory neuronopathies and clearly different from the ultrasound findings in axonal neuropathy.Smaller nerves are possibly a distinctive finding in SBMA that may distinguish it from other motor neuron syndromes. Further studies are warranted to confirm this and determine the optimal sonographic protocol.

Neuromuscular ultrasound as a marker for inherited sensory neuronopathy

“…Eight papers that used ultrasound in various inherited diseases with sensory neuronopathies were identified. [2][3][4]6,8,9,12,13 On further selection, a study of nerve ultrasound in Friedreich ataxia was excluded. 12 We also excluded a preliminary report on seven patients with CANVAS, 2 who were subsequently included in a larger study conducted by the same authors.…”

“…This distinctive ultrasound pattern was first discovered in cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) 2,3 and subsequently confirmed in other inherited sensory neuronopathies, such as those in some types of SCA, [4][5][6] mitochondrial diseases, 7 and, more recently, SBMA. 8,9 Because more than 90% of the total axons in the mixed upper limb nerves are sensory, it is plausible that a severe loss of these axons secondary to dorsal root ganglion cell loss results in visible nerve shrinkage. 10,11 These studies suggest that ultrasound could be a useful diagnostic or follow-up marker for inherited sensory neuronopathy.…”

Ultrasound of peripheral nerves distinguishes inherited sensory neuronopathy of cerebellar ataxia with neuropathy and vestibular areflexia syndrome from inherited axonopathy

“…The “small” nerve CSA abnormality was first discovered in CANVAS, 7,8 but subsequently reported in neuronopathies associated with other inherited diseases, such as spinocerebellar ataxias, 9,11 mitochondrial disorders, 24 and spinal and bulbar muscular atrophy, 10,25 suggesting that this is a distinctive feature of inherited neuronopathies in general.…”

“…Recent studies have shown that ultrasound of the peripheral nerves is a useful tool to differentiate inherited sensory neuronopathies from acquired axonal neuropathies. In contrast to the ultrasound changes reported in polyneuropathy, which most commonly consist of varying degrees of nerve thickening, 1–6 in inherited sensory neuronopathy the nerve size is significantly reduced, being, on average, approximately half the size of nerves in healthy controls and about one third the size of nerves in axonal neuropathy patients 7–11 . This has major clinical implications, as exemplified by the fact that up to one third of patients with chronic idiopathic axonal polyneuropathy (which accounts for 25% to 32% of the polyneuropathies in those over 65 years of age) and tends to affect predominantly the sensory nerves may harbor bi‐allelic replication factor complex subunit 1 (RFC1) expansions 12–14 ; many of these patients would not have been suspected of having sensory neuronopathies on the basis of current clinical or electrophysiological criteria 15 …”

“…degrees of nerve thickening, [1][2][3][4][5][6] in inherited sensory neuronopathy the nerve size is significantly reduced, being, on average, approximately half the size of nerves in healthy controls and about one third the size of nerves in axonal neuropathy patients. [7][8][9][10][11] This has major clinical implications, as exemplified by the fact that up to one third of patients with chronic idiopathic axonal polyneuropathy (which accounts for 25% to 32% of the polyneuropathies in those over 65 years of age) and tends to affect predominantly the sensory nerves may harbor bi-allelic replication factor complex subunit 1 (RFC1) expansions [12][13][14] ; many of these patients would not have been suspected of having sensory neuronopathies on the basis of current clinical or electrophysiological criteria. 15 In previous ultrasound studies of inherited sensory neuronopathy, however, comparisons were made exclusively with acquired types of axonal neuropathy.…”