The Role of Neuromuscular Ultrasound in the Diagnosis of Peripheral Neuropathy

Abstract

The classification of peripheral neuropathies has traditionally been based on etiology, electrodiagnostic findings, or histopathologic features. With the advent of modern imaging, they now can also be characterized based on their varied distribution of imaging findings. We describe the major morphologic patterns of these changes, which include homogeneous enlargement; homogeneous thinning; focal, multifocal, and segmental enlargement; and focal thinning and beading (multifocal thinning). Representative disorders in each of these categories are discussed, along with examples of the more complex imaging manifestations of neuralgic amyotrophy, nerve transection, and hereditary amyloidosis. An appreciation of the diverse morphologic manifestations of neuropathy can help neuromuscular clinicians conduct appropriate imaging studies with ultrasound and, when needed, order suitable investigations with magnetic resonance neurography.

Keywords

electromyography - nerve conduction studies - motor neuron disease - fasciculations - neuralgic amyotrophy

This review discusses how imaging can enhance diagnostic testing for neuromuscular clinicians. It focuses on ultrasound, a technique within their scope of practice.[1] Many of the findings described in this review also can be identified with magnetic resonance (MR) imaging, which is useful for imaging deeper structures such as the lumbosacral plexus and branches of cranial nerves,[2] [3] and is more sensitive in detecting early changes of muscle denervation.[4] Further discussion of MR, which is costly and lacks the ultra-high resolution of ultrasound for the study of nerve,[5] is available in other sources.[2] [3] [4] [6] Recent guidelines for reporting MR findings in neuropathies are likely to enhance its availability for routine clinical use,[7] and ongoing technical advances continue to enhance its role in neuropathy research.[8] [9]

Size, or more practically, cross-sectional area (CSA), is the simplest feature of nerves to characterize with ultrasound. This review divides nerves into four major size categories: mild, moderate, and marked enlargement, and thinning, and two major distribution categories: homogeneous and heterogeneous. Currently, there is no formal consensus on how to precisely define these categories. As a guiding principle, nerve CSA consistently increased by 1 to 1.5 times the upper limit of normal can be considered moderately enlarged, while greater increases in CSA can be considered marked enlargement. Mild nerve enlargement implies that almost all measures at individual nerve sites are at or above the reference means and some modestly exceed the upper limits of normal. Homogeneous enlargement can be defined by nerves in which CSA varies no more than 50% in adjacent segments or side to side (at noncompression sites), whereas heterogeneous enlargement involves a variation of greater than 50%. Several ultrasound rating scales for nerves have been published, which provide specific, albeit different, rules for scoring nerve enlargement, and these are cited where they have shown value. While promising, these scales have yet to be widely adopted, and further validation is needed. It should also be noted that nerve size is associated with body size and BMI, such that larger adults have slightly larger nerves than smaller adults.[10] Similarly, nerve size in children is smaller, often in proportion to body size; reference values for nerve size in children have been published separately.[11]

Electrodiagnosis and nerve imaging are complementary and highlight different aspects of nerve pathology. Electromyography (EMG) and nerve conduction studies (NCS), which primarily evaluate physiology, tend to better characterize the severity and duration of a disorder, assess function, and distinguish neuropathic from myopathic causes.[12] [13] Imaging, which primarily evaluates anatomy, tends to better localize lesions, assess adjacent tissues that contribute to nerve dysfunction, and map the distribution of nerve and muscle findings.[14] [15] Findings from the two techniques are often additive. For example, disorders with nerve enlargement often show slowing of nerve conduction velocity and/or conduction block, whereas those with thinning of nerves show reduced or absent compound muscle action potentials (CMAPs) or sensory nerve action potentials (SNAPs).[16] [17] Recognizing their synergy, several instrument manufacturers currently produce instruments capable of performing both electrodiagnosis and ultrasound. Readers interested in ultrasound instrumentation or methods of clinical application are referred to available comprehensive sources.[12] [18] [19] [20] [21] Those interested in acquiring hands-on skills are encouraged to participate in training courses, which too are now widely available.[22]

Patterns of Nerve Involvement Apparent by Ultrasound

Homogeneous Nerve Enlargement and Thinning

Marked Homogeneous Nerve Enlargement

Among disorders with marked homogenous nerve enlargement, Charcot–Marie–Tooth (CMT) disease type 1A is the most common in neuromuscular practice. The increased nerve size in CMT1A is associated with histopathologic findings of larger fascicles, increased endoneurial connective tissue, and onion bulb formation.[23] On ultrasound, the nerves are hypoechoic with large fascicles. The CSAs of the nerves are enlarged throughout, with perhaps a slightly greater degree of enlargement as one traverses a limb from distal to proximal.[16] [24] [25]

Noonan's syndrome[26] [27] is another disorder in this category, notable in that the nerves may be enlarged so significantly that compression at nonentrapment sites can occur.[28] Other disorders with marked homogenous nerve enlargement are listed in [Table 1]. Clinicians familiar with this group of hypertrophic neuropathies may recognize them without imaging, even by palpation; however, if not already considered, ultrasonography of any limb nerve in such patients can suggest the correct diagnosis.

Table 1 Homogeneous nerve abnormalities

	Degree of abnormality	Disorder	Other nerve or muscle findings by ultrasound	Other tissue/organ findings by ultrasound
Homogeneously enlarged nerves
	Marked	Noonan syndrome
		CMT type 1A	Slightly pronounced proximally
		CMT other demyelinating forms
		MLD
		Krabbe disease	Treatment reduces nerve size
	Intermediate
		Other axonal forms of CMT
	Mild
		Diabetes type 1 neuropathy	May predominate at entrapment sites
		Diabetes type 2 neuropathy	Increased nerve blood flow—mild
		Alcohol related	(Based only on MRI findings)
		Uremic	Increased nerve blood flow—mild
		Friedreich ataxia	More prominent in upper limbs
		Critical Illness neuropathy
Homogeneous nerve thinning
	Intermediate
		SBMA (Kennedy's disease)	Fasciculations of muscle	Fatty liver disease
	Mild	ALS	Fasciculations of muscle	Fatty liver disease
		SCA
		HSN
		CANVAS
		Mitochondrial neuropathy (variable findings)

Abbreviations: ALS, amyotrophic lateral sclerosis; CANVAS, cerebellar ataxia with neuropathy and vestibular areflexia syndrome; CMT, Charcot–Marie–Tooth; HSN, hereditary sensory neuropathy; MLD, metachromatic leukodystrophy; SBMA, spinobulbar muscular atrophy; SCA, spinocerebellar ataxia.

Moderate Homogeneous Nerve Enlargement

This group is not defined in detail as it mainly consists of a diverse group of intermediate variants of CMT, both axonal and demyelinating, which have yet to be systematically characterized with ultrasound.[29] Individuals found to have moderate nerve enlargement on ultrasound are likely to benefit from screening for signs of neuropathy in other family members and genetic testing.

Mild Homogenous Nerve Enlargement

Diabetic neuropathy is the major disorder in the category of mild and diffusely enlarged nerves.[30] However, imaging is limited in its ability to distinguish patients with diabetic neuropathy, diabetes without neuropathy, and physiologic nerve enlargement associated with excessive weight. From a patient care standpoint, the diagnosis and treatment of diabetic neuropathies often do not require specialized neurodiagnostic testing. Awareness of nerve ultrasound findings in diabetic neuropathy is important when assessing for potential cooccurring nerve disorders such as compression neuropathies, and in differentiating diabetic polyneuropathy from an inflammatory neuropathy which may respond to treatment.

Diabetic neuropathy itself is heterogeneous. Compared with type 2 diabetes mellitus, type 1 tends to be associated with less nerve enlargement and has a somewhat greater predilection for entrapment sites, particularly at the carpal tunnel.[30] One potential difference, yet to be studied in type 1 diabetes mellitus, is that in type 2 diabetes mellitus there is increased intraneural blood flow as assessed with Doppler.[31] This is seen in 28% of patients at a nonentrapment site and it correlates with neuropathy severity and nerve enlargement.[31] Of interest, similar findings are present in uremic neuropathy.[32] Ultrasound has shown potential as a screening tool for these neuropathies in that it can quickly and painlessly detect enlargement of the tibial nerve at the ankle and thinning of the extensor digitorum brevis muscle,[33] [34] but further study is necessary before recommending ultrasound in routine care of diabetic neuropathy.

Mild and Moderate Homogenous Thinning of Nerves

A reduction of nerve CSA, referred throughout as “thinning,” is much less common than enlargement as a marker of disease. Thinning is thought to primarily reflect a loss of axonal fibers within a nerve without associated inflammation.[35] Thinning may be difficult to recognize, as nerve enlargements are the most common imaging findings. Median nerve CSA measuring 4 mm² or less at the forearm in an adult is suggested as a finding which should prompt consideration of nerve thinning.[36] [37]

Thinning can be a prominent feature in some hereditary neuronopathies, such as cerebellar ataxia with neuropathy and vestibular areflexia syndrome or certain spinocerebellar ataxias[36] [37] [38] [39]; however, in Friedreich ataxia, nerves tend to be mildly enlarged.[40] Neuropathies associated with mitochondrial disorders may demonstrate diffuse thinning, or less frequently diffuse enlargement, even within the same genetic variant.[41] Subtle nerve thinning is found commonly in amyotrophic lateral sclerosis (ALS).[18] While it is rarely specific enough to help in its diagnosis, it can be useful in distinguishing it from mimics known to have enlarged nerves such as multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating neuropathy (CIDP).[42] [43]

Moderate and more definitive nerve thinning is a feature of spinobulbar muscular atrophy (SBMA), also known as Kennedy's disease.[44] SBMA is a rare form of X-linked recessive motor neuron disease caused by a trinucleotide repeat expansion of the androgen receptor gene.[44] While it resembles a lower motor neuron form of ALS, it typically has a later age of onset, slower rate of progression, and involves prominent sensory loss with a marked reduction or absence of SNAPs on NCS. It seems likely that it is the combined loss of both motor and sensory axons that leads to the more marked reduction of nerve CSA in SBMA than in ALS.[44]

Muscle ultrasound proves useful in the diagnosis of both SBMA and ALS because it is highly sensitive to the detection of fasciculations, particularly in deeper muscles where they are not apparent by visual inspection.[45] Fasciculations may be one of the first manifestations of evolving disease in both groups of patients[46] and may prove helpful in identifying otherwise as yet asymptomatic gene carriers as subjects for preventative clinical trials.

Heterogeneous Nerve Enlargement and Thinning

Unifocal Nerve Enlargement

Now that reference values are widely available,[47] [48] [49] unifocal nerve enlargement is an easily recognized ultrasound pattern, a finding first reported in carpal tunnel syndrome[50] and subsequently determined to be a characteristic feature of all entrapment neuropathies.[21] In fact, rigorous levels of evidence currently support the utility of ultrasound imaging in detecting nerve enlargement for the diagnosis of both carpal tunnel syndrome and ulnar neuropathy at the elbow.[51] [52] In many cases, focal nerve enlargement is accompanied by a mild increase in intraneural blood flow, detectable with Doppler imaging, often termed “hypervascularity.”[21] That both nerve enlargement and increased blood flow diminish in response to effective therapy with steroid injections and/or carpal tunnel release surgery provides evidence that, in addition to being diagnostic, they are also responsive biomarkers of pathology.[53] [54] Like NCS findings, however, nerve enlargement often does not completely resolve after treatment.[53] [54]

Entrapment neuropathy is also associated with abnormal nerve mobility with flexion and extension of the joints. Nerve mobility is decreased in carpal tunnel syndrome.[55] In ulnar neuropathy at the elbow, the role of hypermobility, nerve dislocation, and subluxation are debated as being protective or provocative factors.[56] Recent consensus guidelines have concluded that the combined use of ultrasound and NCSs, because they provide independent measures of nerve pathology, are optimal for diagnostic accuracy in carpal tunnel syndrome and ulnar neuropathy at the elbow.[12] [13] [14]

Imaging is particularly helpful in patients with atypical features of a suspected entrapment neuropathy. For example, patients presenting with symptoms of carpal tunnel syndrome primarily in the nondominant hand are likely to have other findings of pathology by imaging studies, including tenosynovitis or anatomic variants which help inform treatment options.[15] Patients with fibular neuropathy at the knee, but without an obvious cause such as leg crossing, weight loss, or prolonged squatting, are more likely to have an unexpected intraneural ganglion cyst.[57]

Of note, ultrasonographic nerve enlargement is less frequently observed in radial neuropathy at the spiral groove. In this mononeuropathy, the presence of nerve enlargement has prognostic significance, as patients with nerve enlargement on ultrasound were found to have less strength recovery at 3 months compared to those without ([Fig. 1]).[58] It may be that the nerve injury in acute nerve compression and ischemia, such as can be seen in typical cases of “Saturday night palsy,” differs from that in nerves exposed to more chronic forms of compression, but further studies are needed.

Fig. 1 Long-axis image of the radial nerve, demonstrating enlargement at the spiral groove in a patient who awoke with acute wrist drop. At the region of enlargement, there is a loss of fascicular architecture. The diameter at caliper 3 is 2.25 mm (arrowhead), while 1 and 2 measure 1.62 and 1.53 mm, respectively. Electrodiagnostic findings confirm radial neuropathy at the spiral groove, with a conduction block across the elbow. H, humerus.

While entrapment is by far the most common cause of focal nerve enlargement, other disorders, some discussed in the sections below, may initially manifest as such, even at entrapment sites, as part of a more extensive nerve disorder. Nerve tumors, both intrinsic and metastatic, can also present in this fashion. Readers interested in the differential diagnosis and protean imaging features of tumors are referred to the surgical literature where they are covered in detail.[59]

Unifocal Nerve Thinning and Transection

Another simple, focal disorder to recognize with imaging is unifocal thinning, commonly referred to in the ultrasound literature as a “notch” sign. This is usually seen in association with severe extrinsic nerve compression by an adjacent lesion such as a pseudoaneurysm.[60] It is rare and perhaps most commonly encountered in patients after failed carpal tunnel repair in which residual transverse carpal ligament, which was not fully transected, compresses the median nerve acutely, or when scar tissue compresses the median nerve, chronically, at the surgical site ([Fig. 2]).[61] Compression severe enough to cause marked nerve thinning is typically accompanied by the absence or marked reduction of respective CMAP and SNAP on NCS.

Fig. 2 This is a long-axis image of the median nerve (N) in a patient following a failed carpal tunnel decompression (proximal to the left, also, note the tendon (T) below the nerve, which is unaffected). Postoperatively, nerve conduction studies were compatible with severe axonal loss and were more abnormal than the preoperative studies. Note the prominent notch sign (arrow) and that the nerve is hyperechoic at that point. During the subsequent repair, scar tissue was found to be compressing the nerve.

Nerve discontinuity from traumatic nerve transection is a challenging imaging finding in which distal and proximal segments of the nerve are separated. Acute transection can be difficult to appreciate due to tissue swelling, hemorrhage, and distorted anatomy. Because electrodiagnostic testing cannot distinguish between nerve transection and severe axonal injury with nerve continuity, and because transection responds best to immediate surgical correction, emergent imaging with ultrasound or MRI is indicated whenever suspected.[62] Each test has advantages. Ultrasound may be superior in suspected nerve injury with nearby metal hardware, but the choice between MR and ultrasound is partially dictated by availability.[63] Of interest, apparent nerve discontinuity on ultrasound may be a sequela of remote bone fracture, in that callous formation may encase a segment of continuous nerve but block the ability to visualize it with ultrasound. In such cases, the nerve is not truly discontinuous and, if followed, can be seen to enter and then reemerge from the callous at a distant site. Nerve function may be impaired or remain fully intact in such cases.[64]

Multifocal and Segmental Nerve Enlargement

Because of their patchy nature, disorders associated with multifocal and segmental nerve enlargement often require an evaluation of multiple nerves to assess fully. Furthermore, as indicated earlier, multifocal disorders may initially present with symptoms at a single site. In patients with features of atypical focal neuropathy, unexplained systemic symptoms, or focal neuropathy that evolves in a nonentrapment site, consideration should be given to screening for a more widespread condition. The following sections highlight disorders that may present in this fashion.

Multifocal and Segmental Nerve Enlargement—Predominantly at Nonentrapment Sites

Acquired inflammatory and immune-mediated neuropathies, especially demyelinating neuropathies, often display moderate to marked nerve enlargement. Ultrasound imaging may demonstrate nerve enlargements along multiple regions of a single or multiple peripheral nerves, outside of entrapment sites ([Fig. 3]). Regions of enlargement may be accompanied by increased Doppler signal representing increased intraneural vascularity.[65] [66] [67] The diagnostic utility of imaging for CIDP is well established,[16] [68] [69] and current guidelines recommend nerve ultrasound in patients with possible CIDP.[70] Similar multifocal enlargements are seen in disorders such as MMN,[71] [72] POEMS syndrome,[73] [74] [75] [76] anti-myelin-associated glycoprotein (anti-MAG) neuropathy,[77] [78] [79] [80] and others ([Table 2]).[81] [82] Ultrasound can also assist with the diagnosis of Guillain–Barre syndrome (GBS),[83] [84] which, in contrast to CIDP, tends to feature proximal segmental involvement with less significant peripheral nerve enlargement.[68]

Fig. 3 Panel A depicts the median nerve in the proximal forearm taken from a patient with CIDP. The CSA is enlarged, measuring 18 mm². Panel B is taken from the same location in a healthy control; the CSA is 7 mm². Panel C is from another patient with CIDP. The median nerve is 10 mm², but there are several enlarged fascicles. FDP, flexor digitorum profundus muscle; FDS, flexor digitorum superficialis muscle; FCR, flexor carpi radialis muscle.

Table 2 Heterogeneous nerve abnormalities: focal, multifocal, and segmental

Morphologic finding	Disorder	Other nerve ultrasound features	Ultrasound findings in other tissues
Segmental nerve enlargement (nonentrapment sites)
	CIDP	Nerve echogenicity may reflect chronicity
	MMN
	POEMS	Nerve echogenicity may be increased	Organomegaly
	Wartenberg's migrant sensory neuritis
	GBS	May be subtle at the time of presentation
	Anti-MAG neuropathy
	Sjogren's syndrome		Associated parotid gland findings
Multifocal manifest prominently at entrapment sites
	HNPP
	ALD	May have regional, proximal enlargement
	ATTRv	Proximal nerve and brachial plexus enlargement
	Fabry disease
	Diabetes (see [Table 1])
Multifocal enlargement at nonentrapment sites
	Sarcoid
	Lepromatous	Marked increase in intraneural blood flow Thickened epineurium
	Lyme
	Neurolymphomatosis	Marked increase in intraneural blood flow “Fried egg sign”
	Vasculitis
	Neoplasm (not reviewed)
Focal enlargement at the entrapment site
	Entrapment neuropathy	May see mild increased intraneural blood flow	Abnormal adjacent tissue may be causative
	(Neoplasms—not reviewed)
Focal thinning (notch sign)
	Severe compression
Nerve discontinuity
	Traumatic transection
	Encasement in bony callous		Nerve enters and exits bone callous

Abbreviations: ALD, adrenoleukodystrophy; ATTRv, hereditary transthyretin amyloidosis; CIDP, chronic inflammatory demyelinating polyneuropathy; GBS, Guillain-Barre syndrome; HNPP, hereditary neuropathy with liability to pressure palsies; MAG, myelin-associated glycoprotein; MMN, multifocal motor neuropathy; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder.

Regions of nerve enlargement do not always correlate with the location of a conduction block found on NCSs, and can occur anywhere along the length of a nerve ([Fig. 4]).[85] As such, in patients with suspected acquired demyelinating neuropathy, scanning the brachial plexus and peripheral nerves along their entire course, with the use of Doppler at areas of enlargement, is recommended.

Fig. 4 This is a patient with longstanding CIDP showing a short-axis ultrasound image of the median nerve (MN) in the axilla, where it is markedly enlarged with a CSA of 72 mm². Note that the nerve is heterogeneously hyperechoic, but that distinct fascicles are hard to visualize. Ultrasound of the median nerve lower in the arm, just proximal to the antecubital fossa (not shown) shows a similar variation in echo intensity and an even larger CSA of 102 mm². This variation in size and echogenicity is distinctly different from findings in CMT1A, in which nerve enlargement occurs, but the enlargement is more uniform throughout the course of the nerve, fascicles tend to remain distinct, and the nerve is homogeneously hypoechoic.

Several composite scoring systems are available to grade the pattern and extent of peripheral nerve enlargement in CIDP. The Ultrasound Pattern Sum Score (UPSS) is sensitive (80%) and specific (93–95%) for CIDP.[68] [69] A different scale, the Bochum ultrasound score, has been shown to accurately differentiate acute-onset CIDP from AIDP.[86] [87] An adjusted Bochum ultrasound score has high specificity for CIDP when electrodiagnostic studies suggest possible or probable CIDP.[88] In GBS, nerve enlargements may be visualized in the brachial plexus. Measurements of the vagus nerve ([Fig. 5]) and the C5 and C6 nerve roots make up a subscore of the UPSS, the UPS-B.[68] In one study, an increased UPS-B with a normal UPSS score had a positive predictive value of 85% for the diagnoses of GBS.[68]

Fig. 5 Short-axis view of the vagus nerve. The image in Panel A is taken from a patient with GBS. Note the enlarged vagus nerve with a CSA of 5 mm². Panel B is a healthy control; the CSA of the vagus nerve is 2 mm². T, thyroid gland; JV, jugular vein (compressed); CA, carotid artery; SCM, sternocleidomastoid muscle; A. scalene, anterior scalene muscle.

As discussed earlier, nerves are diffusely and homogeneously enlarged in disorders such as in CMT1A. Ultrasound imaging scores that assess homogeneity or intranerve variability[16] [89] can help differentiate the multifocal and segmental nerve enlargement seen in CIDP from the changes in CMT1A, which also are not associated with increased intraneural blood flow seen on Doppler.[66] [67]

The response of ultrasound findings to treatment of CIDP is variable. Increases in nerve enlargement despite effective treatment have been described,[90] [91] but other reports have shown nerve enlargements to decrease following treatment.[92] [93] Another study has demonstrated both trends among different subgroups.[85] Study methodology and varying pathologic mechanisms of nerve enlargement may explain these heterogeneous outcomes. Further studies are needed to determine how best to use ultrasound to inform treatment. Of note, in refractory and progressive forms of CIDP, the nerves continue to enlarge, a finding that can be helpful when electrodiagnostic findings, such as conduction velocity slowing or conduction block, are obscured by progressive axonal loss.[94]

The ability to distinguish different types of chronic inflammatory neuropathies with nerve ultrasound is limited. Nerve enlargements in POEMS and MMN are less marked compared to CIDP,[68] [72] [73] [75] leading to relatively lower UPSS scores. Increased echogenicity of intraneural connective tissue may be more suggestive of POEMS than CIDP.[76] Of interest, ultrasound may be used to detect hepatosplenomegaly or lymphadenopathy in POEMS. Ultrasonographic findings in anti-MAG neuropathy are similar to CIDP.[77] [78] [79] [80]

Less Pervasively Distributed Forms of Multifocal or Segmental Enlargement

A variety of other inflammatory and infectious neuropathies demonstrate focal or segmental nerve enlargements. Compared to the previously mentioned demyelinating inflammatory neuropathies, conditions in this category tend to have enlargements affecting fewer nerves. Although subject to exception, ultrasound nerve enlargements within this category are more often mild or moderate. These enlargements are notable given predominantly axonal electrodiagnostic findings, which may reflect inflammation. The imaging differences between these categories may be due to differing pathophysiology, or greater likelihood of their discovery prior to more extensive nerve involvement, but imaging data are limited in these disorders. It is unknown how effective imaging is in the identification of asymptomatic lesions or differential diagnosis of these conditions, including sarcoidosis, Lyme disease, and vasculitis. The finding of markedly increased intraneural blood flow on Doppler ultrasound, however, is noteworthy and suggestive of neurolymphomatosis or lepromatous neuropathy.

Neurolymphomatosis is a rare cause of mononeuropathy or multiple mononeuropathies caused by the invasion of neural tissue by tumor cells. It is associated with non-Hodgkin's lymphoma and leukemia.[95] [96] In neurolymphomatosis, nerves become markedly enlarged and hypoechoic in regions corresponding to abnormalities on electrodiagnostic testing, and in the presence of axonal loss. The prominent increase in vascularity is characteristic of neurolymphomatosis, with 90% of cases demonstrating increased flow on Doppler.[95] The “fried-egg sign” describes hyperechoic interior nerve fascicles, surrounded by an outer layer of reduced echo intensity. This is another unique feature of neurolymphomatosis,[96] noted to be present in 63% of the reviewed cases.[97]

Lepromatous neuropathy is a disorder of global prevalence[98] that commonly presents as a mononeuropathy or multiple mononeuropathies. The organism has a predilection for cooler body regions, commonly affecting the ulnar nerve at the elbow and fibular nerve at the knee.[98] In addition to nerve enlargement and increased vascularity,[99] [100] thickened epineurium may also be seen.[101] Using the linear calipers at the thickest site of hyperechoic epineurium provides a distance measurement that can be compared to established normative values.[99] Of interest, nerve ultrasonography may be able to identify asymptomatic disease in the household contacts of leprosy patients.[98]

Neuropathies due to Lyme disease, systemic vasculitis, sarcoidosis, and Sjogren's syndrome can show nerve enlargements, but currently, expected findings with Doppler ultrasound are not well described in these conditions.[81] [102] [103] [104] [105] Other notable ultrasound features to consider include the distal predominance of enlargement, which has been described in sarcoidosis,[104] and fascicular changes, which may be prominent in vasculitic neuropathy.[103] In suspected Sjogren's syndrome, ultrasound can detect increased vascularity and loss of the normal homogenous ground-glass appearance in the salivary glands, which can assist in confirming the diagnosis.[106] [107]

Multifocal Nerve Enlargement, Predominantly at Entrapment Sites

A subtype of CMT, autosomal dominant hereditary neuropathy with liability to pressure palsies (HNPP), is perhaps the most characteristic disorder in this group. HNPP features prominent nerve enlargement on ultrasound, typically with normal imaging between areas of entrapment.[108] [109] [110] [111] Although distinguishable by ultrasound from CMT1A, which shows a homogeneous enlargement of nerves along their course, HNPP is not the only disorder with a predilection for entrapment sites. Similar but less marked nerve enlargement at these locations can also be seen in Fabry disease,[111] and variable nerve enlargement, particularly proximally, is seen in adrenoleukodystrophy.[112] Hereditary amyloidosis may also show this pattern, but it has other complex manifestations which are further discussed later. And, as mentioned earlier, both type 1 and 2 diabetes mellitus can also show nerve enlargements with a predilection for entrapment sites.

Heterogeneous Enlargement or Thinning Restricted to Nerve Segments or Nerve Regions

Recent studies have demonstrated that in some disorders, segments of nerve enlargement may be confined to the distribution of a single nerve or a single region through which several nerves pass. This contrasts with the multifocal autoimmune neuropathies which typically affect multiple nerves at varying sites. The most striking examples of selective segmental/regional enlargement occur following severe, acute nerve trauma.[113] [114] With gunshot wounds, the enlargement is prominent in the distal portion of the nerve. Nerves not directly in the path of the injury but close enough to be affected by shock waves and thermal injury may show a similar change, which may persist or slowly abate over time ([Fig. 6]).[113] Following traumatic amputation, proximal portions of the nerve may show prominent, persistent enlargement as well.[114] [115] Other disorders, such as herpes zoster and postradiation neuropathy, can be associated with segmental nerve enlargement limited to the regions affected.[116] [117] After long-term recovery from zoster, however, nerve thinning may be seen.[118] Of interest, the vagus nerve may show segmental enlargement following COVID-19 infections[119] or in GBS, in which case it may herald the development of dysautonomia.[120]

Fig. 6 This patient sustained a bullet wound in the right proximal forearm from a 9-mm handgun causing a proximal median neuropathy. The area of maximal enlargement is 2 cm distal to the bullet entry site. Panel A depicts the median nerve in the long axis, demonstrating enlargement and hypoechogenicity, but preserved axonal continuity. Panel B shows the enlargement in the short axis, where the CSA measures 92 mm² and there is an increased Doppler signal (not shown). PT, pronator teres muscle; FCR, flexor carpi radialis muscle.

Unusual and Complex Patterns of Nerve Morphology: Hereditary Amyloidosis and Neuralgic Amyotrophy

Hereditary transthyretin amyloidosis (ATTRv) is a rare but treatable multisystem disorder with multiple features depending on the genetic variant.[121] [122] Common peripheral nervous system manifestations include polyneuropathy, autonomic neuropathy, and carpal tunnel syndrome.[122] Ultrasound may help identify TTR amyloidosis and can be used to monitor progression in someone with a pathogenic variant. Nerve enlargement has been described at entrapment sites, especially the ulnar nerve at the elbow; other interesting ultrasound findings warrant further comment.

A unique ultrasound finding in ATTRv is the lack of median nerve enlargement seen at the wrist in patients with electrodiagnostically confirmed median neuropathy. Carpal tunnel syndrome is frequently the first symptom of ATTRv, sometimes presenting years before other symptoms develop.[122] [123] [124] Suspicion of amyloidosis at the time of presentation of carpal tunnel syndrome could lead to earlier diagnosis and treatment of ATTR, but the high general prevalence of carpal tunnel syndrome makes this a challenge. This electrodiagnostic and ultrasonographic disassociation has been observed in both ATTRv and wild-type ATTR amyloidosis (ATTRwt) and is a red flag for ATTR ([Fig. 7]).[123] [125] [126] A heightened index of suspicion is warranted if such individuals have other features compatible with ATTRv, such as a history of spinal stenosis, ruptured biceps tendon, or prior entrapment neuropathies.

Fig. 7 The median nerve at the distal wrist crease in a patient with hereditary TTR amyloidosis. The image was obtained using an ultra-high-frequency transducer. The nerve has a normal CSA of 7.4 mm², despite symptoms of carpal tunnel syndrome and electrodiagnostic findings confirming median neuropathy at the wrist. The median motor latency was prolonged at 5.7 ms.

In ATTRv polyneuropathy, in addition to nerve enlargement at entrapment sites, moderate enlargement of proximal nerve segments can be observed on ultrasound.[123] [125] [127] [128] Nerve enlargements tend to be more extensive as the clinical and electrodiagnostic severity of polyneuropathy increases,[125] and these enlargements are notable given the predominantly axonal electrodiagnostic pattern.[128] The median nerve in the axilla and the brachial plexus are more frequently enlarged.[123] [125] [127] [128] Serial studies demonstrate gradual brachial plexus enlargement over time in people with neuropathy due to ATTRv and asymptomatic carriers of the ATTRv gene, raising the possibility that brachial plexus ultrasound may be a biomarker for the disorder.[128]

Polyneuropathy with nerve ultrasound enlargements at entrapment sites is also the pattern in diabetic neuropathy.[30] [127] Evaluation of the vagus nerve is a potential differentiating factor between these conditions. Comparing ATTRv patients to controls, the CSAs of the vagus nerves were found to be increased.[129] In diabetic neuropathy, the CSA of the vagus nerve is not increased compared to controls.[130] [131] At the individual patient level, the utility of the vagus nerve measurement is not established.

As a rare and heterogeneous condition, uncertainties remain. Specific genetic variants may individually have differing ultrasound characteristics. Further studies are required to provide greater characterization and evaluate the utility of ultrasound in the diagnosis of TTR amyloidosis.

Neuralgic amyotrophy (NA) is a syndrome featuring a transient bout of severe shoulder pain followed by multifocal arm weakness.[132] Although NA is a clinical diagnosis, ultrasound or MR imaging assists in diagnosis through the identification of enlargements, constrictions, or fascicular entwinement.[132] [133] [134] Of these associated imaging findings, several appear to be unique, if not pathognomonic for NA. Due to the extent, variety, and specificity of these imaging findings, NA is presented in the complex category. An advantage of imaging in NA is that while it takes weeks for signs of denervation to appear on EMG, hourglass constrictions have been observed as early as 12 hours from symptom onset on ultrasound.[135]

A protocol describing the ultrasound scanning technique in NA has been published.[136] Generally, an ultrasound examination should focus on clinically affected regions based on the history and exam, and in NA this may include evaluation of the nerve roots, brachial plexus, and/or peripheral nerves in the arm.[136] [137] A clinically affected nerve is highly likely (74–90%) to demonstrate at least one abnormality on ultrasound.[133] [134] [135] [137] If there is suspicion of phrenic nerve involvement, an ultrasound evaluation of the diaphragm can be performed.[138] The diagnostic utility of Doppler in NA is currently unknown. Increased Doppler signal within the nerve has been reported,[137] while some have seen no increase in Doppler signal.[139] Differing reports regarding Doppler flow may relate to the chronicity of NA at the time of the ultrasound scan. Fascicular involvement is common in neuralgic amyotrophy. Enlargements and constrictions may be observed in the nerve itself or within individual fascicles.[133] [134] [136] [140] For example, anterior interosseus nerve lesions in NA often localize to a fascicle within the parent median nerve in the upper arm, rather than distally in the forearm.[141]

Enlargements are the most common imaging findings in NA but are the least specific. Compared to constrictions or fascicular entwinements, enlargements may have a better prognosis.[134] If widespread imaging is undertaken, enlargements may be seen in clinically unaffected nerves, even in the contralateral limb.[133] [139] Constrictions can be complete or incomplete, and focal, multifocal, or segmental.[133] [134] [136] Focal constrictions are referred to as hourglass constrictions based on their appearance on longitudinal imaging ([Fig. 8]). Constrictions are less sensitive but more specific for NA, as hourglass constrictions have not been described in other conditions.[134] Multifocal constrictions result in a beaded appearance on imaging. Patients with severe neurogenic changes on EMG are more likely to have constrictions.[142] Fascicular entwinement is the ultrasonographic phenomenon of individual fascicles in a nerve rotating around each other while scanning dynamically in a short-axis view ([Fig. 9]).[134] This was reported in 5 of 70 affected nerves in NA in one series[134] and is specific for NA, as this phenomenon has not been reported in other conditions.

Fig. 8 Long-axis images demonstrating nerve constrictions in patients with neuralgic amyotrophy. Panel A is a nerve fascicle of the radial nerve in the distal upper arm. The fascicle demonstrates proximal enlargement with segmental constriction. Panel B is the anterior interosseous nerve in the proximal forearm, under the pronator teres muscle, demonstrating a focal “hourglass” constriction. H, humerus bone; AIN, anterior interosseous nerve; PT, pronator teres muscle. (Images courtesy of Dr. Juerd Wijntjes.)

Fig. 9 (A) An axial image of the median nerve (MN) at the antecubital fossa in a patient with neuralgic amyotrophy. (B and C) Enlarged images of the same nerve, taken from a video clip demonstrating fascicular entwinement. The transducer is moved very slowly from distal to proximal over a few mm nerve segments in the antecubital fossa; the images are taken 16 frames apart (30/s). Note that while fascicles 1 and 2 rotate clockwise, fascicles 3 and 4 do not, demonstrating that neither a positional change of the transducer nor rotation of the entire nerve has occurred. In neuralgic amyotrophy, the degree of fascicular rotation exceeds that seen in typical nerves, but formal reference values for this phenomenon are not available. BA, brachial artery; SC, subcutaneous tissue.

Pathologic correlation suggests that hourglass constrictions represent nerve torsion.[133] [137] [142] [143] However, the prognostic relevance is not completely understood. Some literature suggests benefits from surgical intervention in such cases,[134] [144] but there have been no randomized controlled trials. A case report described a persistent hourglass constriction in an affected nerve that recovered completely after observation alone.[145]

Ultrasound Patterns Discordant with Electrodiagnostic Features

While ultrasound and electrodiagnostic findings typically are complementary, in some situations discordant results may be informative. Nerve conduction velocity slowing but normal ultrasound can be seen with carpal tunnel syndrome in ATTRv patients. In the neuropathy of autosomal recessive spastic ataxia of Charlevoix-Saguenay, this pattern is similar but more widespread.[146] In contrast, the reverse, with nerve enlargement by ultrasound but normal NCSs, is more likely to be found in Tangier disease.[147]

Discussion

Imaging is integral to neuromuscular medicine, and this review characterizes findings in nerves that can help guide testing and diagnosis. The proposed classification is based on the severity and distribution of enlargement and thinning seen in various neuropathies. This review highlights some conditions in which imaging should be considered, although alternative strategies for diagnostic workup may be appropriate if expertise in ultrasound or MR neurography is not readily available. Ultrasound has advantages over conventional electrodiagnostic testing in the acute phase of nerve transection and NA. It is also advantageous in patients with suspected anatomic variants, implanted electrical devices, marked pain intolerance, or other factors that may interfere with electrodiagnostic testing or nerve and muscle biopsy.

Previous investigators have classified nerve abnormalities in neuropathy with different terminology than used in this report,[148] which is appropriate given their complexity and the absence of a definitive histopathologic grading system for these disorders. Several common disorders, including HIV-related and nutritional neuropathies, have not been systematically explored with imaging, which limits their inclusion in the tables or relevance to differential diagnosis. Another limitation of this report is that it does not account for all the pathologic features detectable by ultrasound. For example, elastography, a technique possible with both MR and ultrasound, can be used to classify what might be considered “stiffness” of nerves[149]; more recent studies with artificial intelligence have begun investigating nerve parameters besides simple enlargement in neuropathy, including assessments of the epineurium, fascicles, and interfascicular tissues.[150] Given the rapid evolution of imaging technology, future discoveries in neuropathy seem likely.

Table 3 Heterogeneous nerve abnormalities: restricted segmental changes

Nerves involved	Nerve abnormality /disorder	Findings in other tissues
Vagus nerve	Enlargement in GBS-related dysautonomia
	Enlargement in post-COVID recovery
	Thinning in Parkinson's disease
Brachial plexus	Enlargement in postradiation plexopathy	Skin atrophy, focal muscle thinning/fibrosis
	Enlargement—acute zoster	Skin swelling
	Thinning—chronic zoster
Peripheral limb nerves	Enlargement of segments distal to amputation
	Enlargement proximal to gunshot wounds
Proximal lower extremity nerves	Enlargement in diabetic amyotrophy

Abbreviation: GBS, Guillain-Barre syndrome.

Table 4 Atypical nerve ultrasound findings

Disorder	Ultrasound findings
Neuralgic amyotrophy	Selective fascicular enlargement, fascicular entwining
	Focal/segmental nerve enlargement; focal or serial areas of nerve thinning (beading)
Hereditary transthyretin amyloidosis	May show enlargement at sites of entrapment and/or segmental enlargement of the brachial plexus and vagus nerve

Table 5 Discordant nerve ultrasound and nerve conduction study findings

Disorder	Discordant NCS/ultrasound findings
ATTRv	NCV slowing with carpal tunnel syndrome but normal nerve ultrasound
ARSACS	Generalized NCV slowing with normal nerve ultrasound
Tangier disease	Diffusely enlarged nerves on ultrasound but normal NCV

Abbreviations: ARSACS, autosomal recessive spastic ataxia of Charlevoix-Saguenay; ATTRv, hereditary transthyretin amyloidosis; NCV, nerve conduction velocity.

Conflict of Interest

None declared.

• References

• 1 Walker FO, Alter KE, Boon AJ. et al. Qualifications for practitioners of neuromuscular ultrasound: position statement of the American Association of Neuromuscular and Electrodiagnostic Medicine. Muscle Nerve 2010; 42 (03) 442-444
• 2 Eajazi A, Weinschenk C, Chhabra A. Imaging biomarkers of peripheral nerves: focus on magnetic resonance neurography and ultrasonography. Semin Musculoskelet Radiol 2024; 28 (01) 92-102
• 3 Baal JD, Yoon D, Patel RP, Chin CT, Shah VN. Advanced imaging of the peripheral nerves, from the AJR “How We Do It” special series. Am J Roentgenol 2024; 1 (01) 1-12
• 4 Deshmukh SD, Samet J, Fayad LM, Ahlawat S. Magnetic resonance neurography of traumatic pediatric peripheral nerve injury: beyond birth-related brachial palsy. Pediatr Radiol 2019; 49 (07) 954-964
• 5 Cartwright MS, Baute V, Caress JB, Walker FO. Ultrahigh-frequency ultrasound of fascicles in the median nerve at the wrist. Muscle Nerve 2017; 56 (04) 819-822
• 6 Pham M, Oikonomou D, Hornung B. et al. Magnetic resonance neurography detects diabetic neuropathy early and with Proximal Predominance. Ann Neurol 2015; 78 (06) 939-948
• 7 Chhabra A, Deshmukh SD, Lutz AM. et al. Neuropathy score reporting and data system (NS-RADS): MRI reporting guideline of peripheral neuropathy explained and reviewed. Skeletal Radiol 2022; 51 (10) 1909-1922
• 8 Lin Y, Tan ET, Campbell G. et al. Improved 3D DESS MR neurography of the lumbosacral plexus with deep learning and geometric image combination reconstruction. Skeletal Radiol 2024; 53 (08) 1529-1539
• 9 Schreiber S, Schreiber F, Peter A. et al. 7T MR neurography-ultrasound fusion for peripheral nerve imaging. Muscle Nerve 2020; 61 (04) 521-526
• 10 Cartwright MS, Passmore LV, Yoon JS, Brown ME, Caress JB, Walker FO. Cross-sectional area reference values for nerve ultrasonography. Muscle Nerve 2008; 37 (05) 566-571
• 11 Abdelnaby R, ELgenidy A, Mohamed KA. et al. Sonographic reference values of nerve size in children: a systematic review and meta-analysis. Muscle Nerve 2023; 67 (03) 217-225
• 12 Preston DC, Shapiro IV BE. eds. Electromyography and Neuromuscular Disorders. Philadelphia: Elsevier; 2023
• 13 Pelosi L, Arányi Z, Beekman R. et al. Expert consensus on the combined investigation of carpal tunnel syndrome with electrodiagnostic tests and neuromuscular ultrasound. Clin Neurophysiol 2022; 135: 107-116
• 14 Pelosi L, Arányi Z, Beekman R. et al. Expert consensus on the combined investigation of ulnar neuropathy at the elbow using electrodiagnostic tests and nerve ultrasound. Clin Neurophysiol 2021; 132 (09) 2274-2281
• 15 Chompoopong P, Preston DC. Neuromuscular ultrasound findings in carpal tunnel syndrome with symptoms mainly in the nondominant hand. Muscle Nerve 2021; 63 (05) 661-667
• 16 Grimm A, Vittore D, Schubert V. et al. Ultrasound pattern sum score, homogeneity score and regional nerve enlargement index for differentiation of demyelinating inflammatory and hereditary neuropathies. Clin Neurophysiol 2016; 127 (07) 2618-2624
• 17 Hobson-Webb LD, Padua L, Martinoli C. Ultrasonography in the diagnosis of peripheral nerve disease. Expert Opin Med Diagn 2012; 6 (05) 457-471
• 18 Ralph JW, Walker FO, Aminoff IV MJ. eds. Aminoff's Diagnosis of Neuromuscular Disorders. Philadelphia: Elsevier; 2024
• 19 Kremkau FW. Sonography: Principles and Instruments. 10th ed.. Philadelphia: Saunders; 2020
• 20 Walker FO, Cartwright MS. eds. Neuromuscular Ultrasound. Philadelphia: Elsevier; 2011
• 21 Baute Penry V, Cartwright MS. Neuromuscular ultrasound for peripheral neuropathies. Semin Neurol 2019; 39 (05) 542-548
• 22 Tawfik EA, van Alfen N, Cartwright MS. et al. Virtual neuromuscular ultrasound courses during COVID-19 pandemic: leveraging technology to enhance learning opportunities. Muscle Nerve 2022; 65 (01) 29-33
• 23 Cellerini M, Salti S, Desideri V, Marconi G. MR imaging of the cauda equina in hereditary motor sensory neuropathies: correlations with sural nerve biopsy. AJNR Am J Neuroradiol 2000; 21 (10) 1793-1798
• 24 Yiu EM, Brockley CR, Lee KJ. et al. Peripheral nerve ultrasound in pediatric Charcot-Marie-Tooth disease type 1A. Neurology 2015; 84 (06) 569-574
• 25 Abdelnaby R, Elgenidy A, Sonbol YT. et al. Nerve sonography in Charcot-Marie-Tooth disease: a systematic review and meta-analysis of 6061 measured nerves. Ultrasound Med Biol 2022; 48 (08) 1397-1409
• 26 Aoki Y, Niihori T, Inoue S, Matsubara Y. Recent advances in RASopathies. J Hum Genet 2016; 61 (01) 33-39
• 27 De Ridder W, van Engelen B, van Alfen N. Neurological features of Noonan syndrome and related RASopathies: pain and nerve enlargement characterized by nerve ultrasound. Am J Med Genet A 2022; 188 (06) 1801-1807
• 28 Draaisma F, Erasmus CE, Braakman HMH. et al. Hypertrophic neuropathy: a possible cause of pain in children with Noonan syndrome and related disorders. Eur J Pediatr 2023; 182 (08) 3789-3793
• 29 Padua L, Coraci D, Lucchetta M. et al. Different nerve ultrasound patterns in Charcot-Marie-Tooth types and hereditary neuropathy with liability to pressure palsies. Muscle Nerve 2018; 57 (01) E18-E23
• 30 Tóth M, Szőke A, Arányi Z. Nerve ultrasonographic findings in diabetes mellitus are determined by anatomical location and type of diabetes. Clin Neurophysiol Pract 2023; 8: 115-122
• 31 Borire AA, Issar T, Kwai NC. et al. Sonographic assessment of nerve blood flow in diabetic neuropathy. Diabet Med 2020; 37 (02) 343-349
• 32 Issar T, Walker S, Arnold R, Poynten AM, Endre ZH, Krishnan AV. Peripheral nerve morphology and intraneural blood flow in chronic kidney disease with and without diabetes. Muscle Nerve 2022; 65 (05) 603-607
• 33 Yavuz K, Yurdakul FG, Guler T, Bodur H. Predictive value of ultrasonography in polyneuropathy diagnosis: electrophysiological and ultrasonographic analysis. Rheumatol Int 2023; 43 (09) 1733-1742
• 34 Severinsen K, Obel A, Jakobsen J, Andersen H. Atrophy of foot muscles in diabetic patients can be detected with ultrasonography. Diabetes Care 2007; 30 (12) 3053-3057
• 35 Pelosi L, Ghosh A, Leadbetter R, Lance S, Rodrigues M, Roxburgh R. Nerve ultrasound detects abnormally small nerves in patients with spinal and bulbar muscular atrophy. Muscle Nerve 2022; 65 (05) 599-602
• 36 Pelosi L, Coraci D, Mulroy E, Leadbetter R, Padua L, Roxburgh R. Ultrasound of peripheral nerves distinguishes inherited sensory neuronopathy of cerebellar ataxia with neuropathy and vestibular areflexia syndrome from inherited axonopathy. Muscle Nerve 2023; 67 (01) 33-38
• 37 Pelosi L, van Alfen N. Neuromuscular ultrasound as a marker for inherited sensory neuronopathy. Muscle Nerve 2023; 68 (05) 718-721
• 38 Leadbetter R, Weatherall M, Pelosi L. Nerve ultrasound as a diagnostic tool for sensory neuronopathy in spinocerebellar ataxia syndrome. Clin Neurophysiol 2019; 130 (04) 568-572
• 39 Pelosi L, Mulroy E, Leadbetter R. et al. Peripheral nerves are pathologically small in cerebellar ataxia neuropathy vestibular areflexia syndrome: a controlled ultrasound study. Eur J Neurol 2018; 25 (04) 659-665
• 40 Di Pietro G, Cioffi E, Falco P. et al. Nerve ultrasound in Friedreich's ataxia: enlarged nerves as a biomarker of disease severity. Clin Neurophysiol 2024; 159: 75-80
• 41 Yong VTY, Kilfoyle D, Hutchinson D, Rodrigues M, Roxburgh R, Pelosi L. Heterogeneity of nerve ultrasound findings in mitochondrial disorders. Clin Neurophysiol 2021; 132 (02) 507-509
• 42 Bunschoten C, Jacobs BC, Van den Bergh PYK, Cornblath DR, van Doorn PA. Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol 2019; 18 (08) 784-794
• 43 Grimm A, Décard BF, Athanasopoulou I, Schweikert K, Sinnreich M, Axer H. Nerve ultrasound for differentiation between amyotrophic lateral sclerosis and multifocal motor neuropathy. J Neurol 2015; 262 (04) 870-880
• 44 Pelosi L, Ghosh A, Leadbetter R, Rodrigues M, Roxburgh R. Small nerves are a distinguishing feature of spinal and bulbar muscular atrophy (SBMA). Neurol Sci 2022; 43 (07) 4575-4576
• 45 Duarte ML, Iared W, Oliveira ASB, Dos Santos LR, Peccin MS. Ultrasound versus electromyography for the detection of fasciculation in amyotrophic lateral sclerosis: systematic review and meta-analysis. Radiol Bras 2020; 53 (02) 116-121
• 46 de Carvalho M, Swash M. Fasciculation potentials and earliest changes in motor unit physiology in ALS. J Neurol Neurosurg Psychiatry 2013; 84 (09) 963-968
• 47 Roll SC, Takata SC, Yao B, Kysh L, Mack WJ. Sonographic reference values for median nerve cross-sectional area: a meta-analysis of data from healthy individuals. J Diagn Med Sonogr 2023; 39 (05) 492-506
• 48 Chang KV, Wu WT, Han DS, Özçakar L. Ulnar nerve cross-sectional area for the diagnosis of cubital tunnel syndrome: a meta-analysis of ultrasonographic measurements. Arch Phys Med Rehabil 2018; 99 (04) 743-757
• 49 Walker FO, Cartwright MS. Neuromuscular Ultrasound. 1st ed.. Philadelphia: Elsevier/Saunders; 2011
• 50 Buchberger W, Schön G, Strasser K, Jungwirth W. High-resolution ultrasonography of the carpal tunnel. J Ultrasound Med 1991; 10 (10) 531-537
• 51 Cartwright MS, Hobson-Webb LD, Boon AJ. et al; American Association of Neuromuscular and Electrodiagnostic Medicine. Evidence-based guideline: neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 2012; 46 (02) 287-293
• 52 Shook SJ, Ginsberg M, Narayanaswami P. et al. Evidence-based guideline: neuromuscular ultrasound for the diagnosis of ulnar neuropathy at the elbow. Muscle Nerve 2022; 65 (02) 147-153
• 53 Cartwright MS, White DL, Demar S. et al. Median nerve changes following steroid injection for carpal tunnel syndrome. Muscle Nerve 2011; 44 (01) 25-29
• 54 Ng AWH, Griffith JF, Tsoi C. et al. Ultrasonography findings of the carpal tunnel after endoscopic carpal tunnel release for carpal tunnel syndrome. Korean J Radiol 2021; 22 (07) 1132-1141
• 55 Lin MT, Liu IC, Chang HP, Wu CH. Impaired median nerve mobility in patients with carpal tunnel syndrome: a systematic review and meta-analysis. Eur Radiol 2023; 33 (04) 2378-2385
• 56 Leis AA, Smith BE, Kosiorek HE, Omejec G, Podnar S. Complete dislocation of the ulnar nerve at the elbow: a protective effect against neuropathy?. Muscle Nerve 2017; 56 (02) 242-246
• 57 Visser LH. High-resolution sonography of the common peroneal nerve: detection of intraneural ganglia. Neurology 2006; 67 (08) 1473-1475
• 58 Kerasnoudis A, Ntasiou P, Ntasiou E. Prognostic value of nerve ultrasound and electrophysiological findings in Saturday night palsy. J Neuroimaging 2017; 27 (04) 428-432
• 59 Amrami KK, Chebrolu VV, Felmlee JP. et al. 7T for clinical imaging of benign peripheral nerve tumors: preliminary results. Acta Neurochir (Wien) 2023; 165 (11) 3549-3558
• 60 Cartwright MS, Donofrio PD, Ybema KD, Walker FO. Detection of a brachial artery pseudoaneurysm using ultrasonography and EMG. Neurology 2005; 65 (04) 649
• 61 Kowalska B. Assessment of the utility of ultrasonography with high-frequency transducers in the diagnosis of postoperative neuropathies. J Ultrason 2015; 15 (61) 151-163
• 62 Padua L, Di Pasquale A, Liotta G. et al. Ultrasound as a useful tool in the diagnosis and management of traumatic nerve lesions. Clin Neurophysiol 2013; 124 (06) 1237-1243
• 63 Sneag DB, Zochowski KC, Tan ET. MR neurography of peripheral nerve injury in the presence of orthopedic hardware: technical considerations. Radiology 2021; 300 (02) 246-259
• 64 Erra C, Granata G, Liotta G. et al. Ultrasound diagnosis of bony nerve entrapment: case series and literature review. Muscle Nerve 2013; 48 (03) 445-450
• 65 Goedee HS, Brekelmans GJ, Visser LH. Multifocal enlargement and increased vascularization of peripheral nerves detected by sonography in CIDP: a pilot study. Clin Neurophysiol 2014; 125 (01) 154-159
• 66 Hildebrand A, Schreiber F, Weber L. et al. Peripheral nerve ultrasound for the differentiation between ALS, inflammatory, and hereditary polyneuropathies. Medicina (Kaunas) 2023; 59 (07) 1192
• 67 Carandang MAE, Takamatsu N, Nodera H. et al. Velocity of intraneural blood flow is increased in inflammatory neuropathies: sonographic observation. J Neurol Neurosurg Psychiatry 2017; 88 (05) 455-457
• 68 Grimm A, Décard BF, Axer H, Fuhr P. The ultrasound pattern sum score - UPSS. A new method to differentiate acute and subacute neuropathies using ultrasound of the peripheral nerves. Clin Neurophysiol 2015; 126 (11) 2216-2225
• 69 Tan CY, Yahya MA, Goh KJ, Shahrizaila N. Nerve ultrasound score in chronic inflammatory demyelinating polyneuropathy. Medicina (Kaunas) 2023; 59 (04) 747
• 70 Van den Bergh PYK, van Doorn PA, Hadden RDM. et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint Task Force-Second revision. J Peripher Nerv Syst 2021; 26 (03) 242-268
• 71 Yoshikawa M, Sekiguchi K, Suehiro H. et al. Nerve enlargement differs among chronic inflammatory demyelinating polyradiculoneuropathy subtypes and multifocal motor neuropathy. Clin Neurophysiol Pract 2023; 8: 228-234
• 72 Merola A, Rosso M, Romagnolo A, Peci E, Cocito D. Peripheral nerve ultrasonography in chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: correlations with clinical and neurophysiological data. Neurol Res Int 2016; 2016: 9478593
• 73 Niu J, Ding Q, Fan J. et al. Nerve ultrasound performances in differentiating POEMS syndrome from CIDP. Neurotherapeutics 2022; 19 (02) 455-463
• 74 Lucchetta M, Pazzaglia C, Granata G, Briani C, Padua L. Ultrasound evaluation of peripheral neuropathy in POEMS syndrome. Muscle Nerve 2011; 44 (06) 868-872
• 75 Ding Q, Li J, Guan Y. et al. Nerve ultrasound studies in POEMS syndrome. Muscle Nerve 2021; 63 (05) 758-764
• 76 Dörner M, Ceanga M, Schreiber F. et al. High-resolution nerve ultrasound abnormalities in POEMS syndrome - a comparative study. Diagnostics (Basel) 2021; 11 (02) 264
• 77 Oka Y, Tsukita K, Tsuzaki K. et al. Nerve ultrasound characteristics of immunoglobulin M neuropathy associated with anti-myelin-associated glycoprotein antibodies. Muscle Nerve 2022; 65 (06) 667-675
• 78 Lucchetta M, Padua L, Granata G. et al. Nerve ultrasound findings in neuropathy associated with anti-myelin-associated glycoprotein antibodies. Eur J Neurol 2015; 22 (01) 193-202
• 79 Athanasopoulou IM, Rasenack M, Grimm C. et al. Ultrasound of the nerves - an appropriate addition to nerve conduction studies to differentiate paraproteinemic neuropathies. J Neurol Sci 2016; 362: 188-195
• 80 Goedee HS, Notermans NC, Visser LH. et al. Neuropathy associated with immunoglobulin M monoclonal gammopathy: a combined sonographic and nerve conduction study. Muscle Nerve 2019; 60 (03) 263-270
• 81 Seeliger T, Bönig L, Gingele S. et al. Nerve ultrasound findings in Sjögren's syndrome-associated neuropathy. J Neuroimaging 2021; 31 (06) 1156-1165
• 82 Herraets IJT, Goedee HS, Telleman JA. et al. High-resolution ultrasound in patients with Wartenberg's migrant sensory neuritis, a case-control study. Clin Neurophysiol 2018; 129 (01) 232-237
• 83 Grimm A, Décard BF, Schramm A. et al. Ultrasound and electrophysiologic findings in patients with Guillain-Barré syndrome at disease onset and over a period of six months. Clin Neurophysiol 2016; 127 (02) 1657-1663
• 84 Abou Hagar A, Negm M, Elshamly S. et al. Electrophysiological studies versus high-resolution nerve ultrasound in diagnosis of Guillain–Barré syndrome. Egypt J Neurol Psychiatr Neurosurg 2024; 60: 27
• 85 Niu J, Li Y, Liu T. et al. Serial nerve ultrasound and motor nerve conduction studies in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2019; 60 (03) 254-262
• 86 Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Nerve ultrasound score in distinguishing chronic from acute inflammatory demyelinating polyneuropathy. Clin Neurophysiol 2014; 125 (03) 635-641
• 87 Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Bochum ultrasound score versus clinical and electrophysiological parameters in distinguishing acute-onset chronic from acute inflammatory demyelinating polyneuropathy. Muscle Nerve 2015; 51 (06) 846-852
• 88 Brünger J, Motte J, Grüter T. et al. Nerve ultrasound distinguishes non-inflammatory axonal polyneuropathy from inflammatory polyneuropathy with secondary axonal damage. Front Neurol 2022; 12: 809359
• 89 Padua L, Martinoli C, Pazzaglia C. et al. Intra- and internerve cross-sectional area variability: new ultrasound measures. Muscle Nerve 2012; 45 (05) 730-733
• 90 Kerasnoudis A, Pitarokoili K, Gold R, Yoon MS. Nerve ultrasound and electrophysiology for therapy monitoring in chronic inflammatory demyelinating polyneuropathy. J Neuroimaging 2015; 25 (06) 931-939
• 91 Härtig F, Ross M, Dammeier NM. et al. Nerve ultrasound predicts treatment response in chronic inflammatory demyelinating polyradiculoneuropathy—a prospective follow-up. Neurotherapeutics 2018; 15 (02) 439-451
• 92 Okhovat AA, Nafissi S, Moradi K. et al. Comparison of clinical, ultrasound, and electrophysiologic changes in chronic inflammatory demyelinating polyneuropathy: a prospective study. J Clin Neurophysiol 2023; 40 (03) 250-257
• 93 Zaidman CM, Pestronk A. Nerve size in chronic inflammatory demyelinating neuropathy varies with disease activity and therapy response over time: a retrospective ultrasound study. Muscle Nerve 2014; 50 (05) 733-738
• 94 Grimm A, Vittore D, Schubert V. et al. Ultrasound aspects in therapy-naive CIDP compared to long-term treated CIDP. J Neurol 2016; 263 (06) 1074-1082
• 95 Vijayan J, Chan YC, Therimadasamy A, Wilder-Smith EP. Role of combined B-mode and Doppler sonography in evaluating neurolymphomatosis. Neurology 2015; 85 (09) 752-755
• 96 Wada A, Uchida Y, Hokkoku K. et al. Utility of nerve ultrasound in the management of primary neurolymphomatosis: case report and review of the literature. Clin Neurophysiol Pract 2023; 8: 92-96
• 97 Lee YC, Huang GS, Chang WC, Hsu YC. Fried egg sign: a typical ultrasonography feature of neurolymphomatosis. J Clin Ultrasound 2021; 49 (08) 878-880
• 98 Luppi AM, Ferreira GE, Prudêncio DL. et al. High-resolution ultrasonography for early diagnosis of neural impairment in seropositive leprosy household contacts. PLoS One 2023; 18 (05) e0285450
• 99 Pirola R, Visser LH, Nasr-Eldin YK, Krzesniak-Swinarska M, Wheat SW, Cartwright MS. Neuromuscular ultrasound in leprosy: a scanning protocol. J Clin Ultrasound 2023; 51 (09) 1529-1535
• 100 Lugão HB, Frade MA, Marques Jr W, Foss NT, Nogueira-Barbosa MH. Ultrasonography of leprosy neuropathy: a longitudinal prospective study. PLoS Negl Trop Dis 2016; 10 (11) e0005111
• 101 Visser LH, Jain S, Lokesh B, Suneetha S, Subbanna J. Morphological changes of the epineurium in leprosy: a new finding detected by high-resolution sonography. Muscle Nerve 2012; 46 (01) 38-41
• 102 Stenør CPM, Mahdaoui SE, Wolfram N. Ultrasonic evidence of mononeuritis multiplex caused by Lyme neuroborreliosis. Muscle Nerve 2022; 65 (01) E4-E6
• 103 Grimm A, Décard BF, Bischof A, Axer H. Ultrasound of the peripheral nerves in systemic vasculitic neuropathies. J Neurol Sci 2014; 347 (1-2): 44-49
• 104 Kerasnoudis A, Woitalla D, Gold R, Pitarokoili K, Yoon MS. Sarcoid neuropathy: correlation of nerve ultrasound, electrophysiological and clinical findings. J Neurol Sci 2014; 347 (1-2): 129-136
• 105 Yoshida T, Nodera H, Kumon Y, Osanai S, Izumi Y, Mizukami H. Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings in painful sensory neuropathy associated with Sjögren's syndrome. Mod Rheumatol 2021; 31 (04) 849-855
• 106 Saied F, Włodkowska-Korytkowska M, Maślińska M. et al. The usefulness of ultrasound in the diagnostics of Sjögren's syndrome. J Ultrason 2013; 13 (53) 202-211
• 107 Walker FO, Cartwright MS, Hunt CH. Managing uncommon and unexpected findings during neuromuscular ultrasound. Muscle Nerve 2021; 63 (06) 793-806
• 108 Hooper DR, Lawson W, Smith L, Baker SK. Sonographic features in hereditary neuropathy with liability to pressure palsies. Muscle Nerve 2011; 44 (06) 862-867
• 109 Bayrak AO, Bayrak IK, Battaloglu E, Ozes B, Yildiz O, Onar MK. Ultrasonographic findings in hereditary neuropathy with liability to pressure palsies. Neurol Res 2015; 37 (02) 106-111
• 110 Goedee SH, Brekelmans GJ, van den Berg LH, Visser LH. Distinctive patterns of sonographic nerve enlargement in Charcot-Marie-Tooth type 1A and hereditary neuropathy with pressure palsies. Clin Neurophysiol 2015; 126 (07) 1413-1420
• 111 Winter N, Vittore D, Gess B, Schulz JB, Grimm A, Dohrn MF. New keys to early diagnosis: muscle echogenicity, nerve ultrasound patterns, electrodiagnostic, and clinical parameters in 150 patients with hereditary polyneuropathies. Neurotherapeutics 2021; 18 (04) 2425-2435
• 112 Rattay TW, Just J, Röben B. et al. Nerve ultrasound characterizes AMN polyneuropathy as inhomogeneous and focal hypertrophic. Orphanet J Rare Dis 2018; 13 (01) 194
• 113 Fagan P, Geiger CD, Chenji G, Preston DC. Neuromuscular ultrasound findings in gunshot wounds. Muscle Nerve 2024; 69 (04) 416-421
• 114 Karabay İ, Demir Y, Köroğlu Ö, Gümrük Aslan S, Aydemir K, Gürçay E. Assessment of lower limb peripheral nerves with ultrasound in patients with traumatic amputation. Turk J Phys Med Rehabil 2021; 67 (03) 357-364
• 115 Hill SC, Baker AR, Barton NW, Wexler LH, Scott LJ. Sciatic nerve: paradoxic hypertrophy after amputation in young patients. Radiology 1997; 205 (02) 559-562
• 116 Wada S, Hirano H, Uehara N. et al. Cervical root enlargement in segmental zoster paresis: a study with magnetic resonance imaging and nerve ultrasound. Intern Med 2022; 61 (15) 2361-2365
• 117 Kim JG, Chung SG. Herpetic brachial plexopathy: application of brachial plexus magnetic resonance imaging and ultrasound-guided corticosteroid injection. Am J Phys Med Rehabil 2016; 95 (05) e67-e71
• 118 Renna R, Erra C, Almeida V, Padua L. Ultrasound study shows nerve atrophy in post herpetic neuralgia. Clin Neurol Neurosurg 2012; 114 (10) 1343-1344
• 119 Lladós G, Massanella M, Coll-Fernández R. et al; Germans Trias Long-COVID Unit group. Vagus nerve dysfunction in the post-COVID-19 condition: a pilot cross-sectional study. Clin Microbiol Infect 2024; 30 (04) 515-521
• 120 Grimm A, Décard BF, Axer H. Ultrasonography of the peripheral nervous system in the early stage of Guillain-Barré syndrome. J Peripher Nerv Syst 2014; 19 (03) 234-241
• 121 Poli L, Labella B, Cotti Piccinelli S. et al. Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy. Front Neurol 2023; 14: 1242815
• 122 Zaki N, Miller NJ, Frosk P, Sharma A. Hereditary transthyretin amyloidosis presenting with carpal tunnel syndrome. CMAJ 2024; 196 (03) E95-E99
• 123 Salvalaggio A, Coraci D, Cacciavillani M. et al. Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers. J Neurol 2021; 268 (01) 189-198
• 124 Fosbøl EL, Rørth R, Leicht BP. et al. Association of carpal tunnel syndrome with amyloidosis, heart failure, and adverse cardiovascular outcomes. J Am Coll Cardiol 2019; 74 (01) 15-23
• 125 Granata G, Luigetti M, Coraci D. et al. Ultrasound evaluation in transthyretin-related amyloid neuropathy. Muscle Nerve 2014; 50 (03) 372-376
• 126 Campagnolo M, Cacciavillani M, Cipriani A. et al. Peripheral nerve involvement in wild-type transthyretin amyloidosis. Neurol Sci 2023; 44 (01) 351-354
• 127 Podnar S, Sarafov S, Tournev I, Omejec G, Zidar J. Peripheral nerve ultrasonography in patients with transthyretin amyloidosis. Clin Neurophysiol 2017; 128 (04) 505-511
• 128 Salvalaggio A, Coraci D, Obici L. et al. Progressive brachial plexus enlargement in hereditary transthyretin amyloidosis. J Neurol 2022; 269 (04) 1905-1912
• 129 Du K, Xu K, Chu X. et al. Vagus nerve ultrasound in transthyretin familial amyloid polyneuropathy: a pilot study. J Neuroimaging 2022; 32 (02) 285-291
• 130 Kotb MA, Bedewi MA, Almalki DM. et al. The vagus nerve cross-sectional area on ultrasound in patients with type 2 diabetes. Medicine (Baltimore) 2023; 102 (51) e36768
• 131 Tawfik EA, Walker FO, Cartwright MS, El-Hilaly RA. Diagnostic ultrasound of the vagus nerve in patients with diabetes. J Neuroimaging 2017; 27 (06) 589-593
• 132 Van Eijk JJJ, Groothuis JT, Van Alfen N. Neuralgic amyotrophy: an update on diagnosis, pathophysiology, and treatment. Muscle Nerve 2016; 53 (03) 337-350
• 133 Arányi Z, Csillik A, Dévay K. et al. Ultrasonographic identification of nerve pathology in neuralgic amyotrophy: enlargement, constriction, fascicular entwinement, and torsion. Muscle Nerve 2015; 52 (04) 503-511
• 134 ArÁnyi Z, Csillik A, DéVay K. et al. Ultrasonography in neuralgic amyotrophy: sensitivity, spectrum of findings, and clinical correlations. Muscle Nerve 2017; 56 (06) 1054-1062
• 135 Ripellino P, Arányi Z, van Alfen N. et al. Imaging of neuralgic amyotrophy in the acute phase. Muscle Nerve 2022; 66 (06) 709-714
• 136 Cignetti NE, Cox RS, Baute V. et al. A standardized ultrasound approach in neuralgic amyotrophy. Muscle Nerve 2023; 67 (01) 3-11
• 137 Wang T, Qi H, Wang Z. et al. The role of ultrasonography in diagnosis of neuralgic amyotrophy. Skeletal Radiol 2023; 52 (07) 1305-1311
• 138 Boon AJ, Litchy WJ. Electrodiagnostic and ultrasound evaluation of respiratory weakness. Muscle Nerve 2024; 69 (01) 18-28
• 139 van Rosmalen M, Lieba-Samal D, Pillen S, van Alfen N. Ultrasound of peripheral nerves in neuralgic amyotrophy. Muscle Nerve 2019; 59 (01) 55-59
• 140 Cejas C, Pastor Rueda JM, Hernández Pinzón J, Stefanoff N, Barroso F. Neuralgic amyotrophy detected by magnetic resonance neurography: subclinical, bilateral, and multifocal brachial plexus involvement. Neurol Res 2023; 45 (03) 283-289
• 141 Pham M, Bäumer P, Meinck HM. et al. Anterior interosseous nerve syndrome: fascicular motor lesions of median nerve trunk. Neurology 2014; 82 (07) 598-606
• 142 Sneag DB, Rancy SK, Wolfe SW. et al. Brachial plexitis or neuritis? MRI features of lesion distribution in Parsonage-Turner syndrome. Muscle Nerve 2018; 58 (03) 359-366
• 143 Glorioso D, Palestini R, Cuccagna C, Lauretti L, Padua L. Nerve torsion as a pattern of parsonage-turner syndrome: literature review and two representative cases. J Clin Med 2023; 12 (13) 4542
• 144 Krishnan KR, Sneag DB, Feinberg JH. et al. Outcomes of microneurolysis of hourglass constrictions in chronic neuralgic amyotrophy. J Hand Surg Am 2021; 46 (01) 43-53
• 145 Mane S, Doi K, Hattori Y, Sakamoto S. Persistent hourglass constriction in recovered anterior interosseous nerve palsy due to neuralgic amyotrophy: a case report. J Hand Surg Asian Pac Vol 2023; 28 (04) 507-511
• 146 Kneer K, Straub S, Wittlinger J. et al. Neuropathy in ARSACS is demyelinating but without typical nerve enlargement in nerve ultrasound. J Neurol 2024; 271 (05) 2494-2502
• 147 Pasquale AD, Leonardi L, Fionda L. et al. Nerve high-resolution ultrasonography in Tangier disease. Muscle Nerve 2019; 59 (05) 587-590
• 148 Zaidman CM, Harms MB, Pestronk A. Ultrasound of inherited vs. acquired demyelinating polyneuropathies. J Neurol 2013; 260 (12) 3115-3121
• 149 He Y, Xiang X, Zhu BH, Qiu L. Shear wave elastography evaluation of the median and tibial nerve in diabetic peripheral neuropathy. Quant Imaging Med Surg 2019; 9 (02) 273-282
• 150 Shinohara I, Inui A, Mifune Y, Nishimoto H, Yamaura K, Mukohara S. et al. Using deep learning for ultrasound images to diagnose carpal tunnel syndrome with high accuracy. Ultrasound Med Biol 2022;48(08):S0301-5629(22)00417-3 Seminars

Publication History

Article published online:
21 October 2024