NEUROIMAGING Ultrasound in Neuromuscular Medicine Ultrasound is highly useful and an integrated complement to history, physical exam, and electrodiagnostic testing for . By Vanessa Baute Penry, MD and Jared Hollinger, MD

Introduction protocols for evaluating scapular winging, diaphragm weak- Neuromuscular ultrasound ness, and brachial plexus pathology have been published.2-4 In (NMUS) continues emerging as this article, we review current uses of NMUS for muscle disease an accessible effective adjunct to and peripheral neuropathies and explore future directions. conventional electrodiagnostics. Use of NMUS adds helpful infor- Muscle Ultrasound mation to the diagnostic picture and can affect management.1 Muscle imaging was among the first uses of NMUS and con- The unique benefits of NMUS include point-of-care dynam- tinues to expand with applications for muscular dystrophies, ic imaging of muscle and nerve, supplemental information myopathies, , and other muscle disor- including vascularity and mobility of structures, muscle and ders. Ultrasound of normal has a heteroge- nerve measurements, superior spatial resolution, and visual neous appearance that is fairly hypoechoic (dark) interspersed guidance for procedures. The advantages of NMUS are that with hyperechoic (bright) areas, representing the normal there is little to no discomfort, which is particularly relevant for fibrous connective tissue within the muscle. In the transverse pediatric cases, and limited expense for the patient. A multi- plane, there is a “starry-sky” appearance because these fibrous disciplinary team including surgeons, neurologists, physiatrists, structures are viewed in cross-section against the darker back- and primary care physicians may specifically request NMUS. ground of muscle fibers (Figure 1A). In the longitudinal plane, Frequently implemented in muscle disease and entrapment the bright fibrous structures run lengthwise, streaking across neuropathies, NMUS use is broadening because studies are the darker muscle fibers (Figure 1B). creating reliable protocols for other areas of neuromuscular Muscle disease can present a diagnostic challenge in clinical disease (NMD). For example, recent well-delineated NMUS practice because of clinical confounders, patchy distribution A B C

Figure 1. Transverse (A) and longitudinal (B) ultrasound of normal biceps muscle. Transverse ultrasound of myopathic biceps muscle (homogeneous, hyperechoic) in acid maltase deficiency (Pompe’s disease) (C).

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of pathology, absence of lab abnormalities, and poor tolerance Echogenicity, vascularity, and anisotropy (variability of of EMG testing. Pathologic patterns on ultrasound imaging echointensity when angle of the ultrasound probe is changed) of muscle may complement a thorough history and physical can also be evaluated with NMUS. In end-stage amyotrophic examination for evaluating myopathic processes. Ultrasound lateral sclerosis (ALS), the affected muscle appears “moth can also increase diagnostic yield by identifying involved mus- eaten” because of increased echogenicity in denervated areas cles. When muscle biopsy is needed, NMUS provides useful intermixed with hypoechoic patchy areas of preserved motor guidance when patchy involvement could otherwise lead to a units. Importantly, this finding is not specific for ALS and may suboptimal nondiagnostic muscle sample. be seen in the muscle with other neurogenic disorders.6

Muscular Dystrophies and Myopathies Peripheral Nerve Ultrasound Characteristic ultrasound findings of muscular dystrophies First used in assessment of carpal tunnel syndrome (still the include loss of normal heterogeneous appearance as muscle is most common use of NMUS), NMUS is easy to use and diag- replaced by fatty fibrous tissue in affected muscles. Dystrophic nostic for many forms of nerve pathology. The sonographic muscles take on a bright, homogenous appearance.5 Deep appearance of a normal peripheral nerve consists of discrete tissue reflections are lost or attenuated in severely affected dys- “honeycomb-like” fascicles encased by a relatively hyperechoic trophic muscles. Similar changes of increased echogenicity may epineurium (Figure 2). Cross-sectional area (CSA) is measured be seen in acute inflammatory myopathies, but in contrast to by placing the ultrasound probe perpendicular to the nerve muscular dystrophies, there are often preserved deep-tissue at the site of maximal enlargement just proximal to the site reflections (Figure 1C).6 of suspected entrapment. The CSA measurements are easy to Distribution of abnormal imaging findings may iden- make and have low interobserver variability even when made tify a specific NMD. For example, inclusion body myositis on different ultrasound devices.11 Other measurements includ- often shows increased echogenicity of the flexor digitorum ing echogenicity, vascularity, and mobility are also recorded. profundus with relative sparing of the flexor carpi ulnaris.7 Facioscapulohumeral muscular dystrophy may show preferen- Entrapment Neuropathies tial involvement of the distal thigh muscles.8 Start by imaging The most implemented and practical use of peripheral muscles that are easily accessible and clinically weak in both nerve ultrasound is evaluation for entrapment neuropa- transverse and sagittal planes. Frequently examined muscles thies of the median, ulnar, and fibular nerves, respectively. include the tibialis anterior and vastus lateralis in the lower Well-established ultrasound techniques for these entrap- extremity and the biceps and deltoid in the upper extremity. ments can be easily studied and practiced in a short period of time.12 A diseased nerve has changes in cross-sectional Diaphragmatic Ultrasound area (increased) and echogenicity (decreased) over time. Another innovative use of NMUS is evaluation of dia- There may also be changes in vascularity on power doppler phragm paralysis. This is especially relevant because of safety ultrasound (increased) caused by local inflammation and concerns in needle EMG of the diaphragmatic musculature. injury, and site-specific changes in nerve mobility (decreased Diaphragm thickness and change in thickness during the in median neuropathy at the wrist, increased in the case of respiratory cycle can be accurately assessed and compared nerve subluxation/dislocation in ulnar neuropathy at the side to side. A practical approach to imaging the diaphragm elbow). Use the “ascending elevator” technique to evalu- can be efficiently implemented in the EMG lab or in the ate the entire nerve, scanning in the axial plane distally to intensive care unit (ICU).3 proximally, looking for focal changes along or outside typi- cal entrapment locations. Assess pathologic areas in the Motor Neuron Disease longitudinal plane as well, taking CSA measurements at the Although, by definition, motor neuron disease is not primar- entrapment site and sites immediately distal and proximal ily a muscle pathology, downstream effects of lower motor so comparisons can be made. Use of NMUS for less com- neuron dysfunction are seen in muscle. The ability to capture mon entrapment neuropathy syndromes including pronator and video record dynamic movements (eg, fasciculations) is teres syndrome, anterior osseous nerve (AIN) syndrome, more sensitive with USNM vs EMG.9 The person being test- posterior interosseous nerve (PIN) syndrome, and traumatic edcan be asked if they feel twitching in a particular area, and neuropathy have also been described.12,13 the ultrasound probe can be placed on that muscle to observe both fasciculations and muscle appearance. Muscle thickness Acquired measurements (using very light pressure on the probe and an Ultrasound findings in chronic inflammatory demyelinat- anatomical landmark) may be decreased in NMD when com- ing (CIDP) have recently been the focus pared with normal values or side-to-side comparison.10 of tremendous interest. Findings include multifocal nerve

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A B

Figure 2: Transverse view of normal median nerve at the distal wrist crease (A) and in the ulnar groove (B). enlargement in noncompressible sites and regional or seg- Hereditary Polyneuropathies mental enlargement in the proximal segments of the medi- The most characteristic finding in hereditary neuropathy an nerve, ulnar nerve and brachial plexus.14 Enlargement in (HN), such as Charcot-Marie-Tooth (CMT) disease is diffuse these areas on NMUS in addition to variability in fascicular nerve enlargement along the entire course of an affected size and echogenicity may aid in differentiating demyelinat- nerve. This is in contrast to the segmental enlargement seen ing from axonal neuropathies.15,16 In multifocal motor neu- in CIDP or focal enlargement seen with entrapment neu- ropathy (MMN), there may be multifocal enlargements in ropathy. The diffuse pattern of nerve enlargement seen in the brachial plexus, median, ulnar or radial nerves, but these HN tends to be more pronounced in demyelinating forms have not been shown to necessarily correlate with elec- of CMT, but both demyelinating and axonal forms have trodiagnostic findings such as conduction block.17 In cases been shown to result in nerve enlargement when compared phenotypically consistent with CIDP or MMN for which to healthy controls.14,20 When CMT is suspected clinically electrodiagnostics have not shown evidence of demyelin- or electrodiagnostically, we recommend distal-to-proximal ation, NMUS may identify nerve enlargement.18 The pres- evaluation of selected affected nerves in the upper and/or ence of multifocal ulnar and median nerve enlargement can lower extremities, with evaluation of CSA at multiple sites to help differentiate MMN from ALS, which significantly alters determine the pattern of enlargement. disease management.19 Other acquired axonal polyneuropathies (eg, idiopathic Conclusion or diabetic polyneuropathy) show either normal cross-sec- There are numerous well-described and established roles tional area or only mild enlargement compared with healthy for NMUS in neuromuscular medicine, making this imag- controls, and these abnormalities may be less apparent on ing modality highly useful and an integrated complement an individual basis.20 to history, physical exam, and electrodiagnostic testing. In We recommend using an “elevator technique” as addition to the uses discussed, NMUS may also be used to described previously, including evaluation along the entire guide accurate injections/localization for lumbar punctures, course of the median and ulnar nerves. If significant vari- occipital nerve blocks, botulinum toxin treatment, and ability in nerve size is seen, measurements should be taken other musculoskeletal procedures. at multiple areas, including those of maximal and minimal Additional innovative and practical uses for NMUS are cross-sectional area, making note of changes in echogenicity, being described and developed at a rapid pace. Examples of vascularity, and fascicular structure. As stated previously, the budding applications include the use of ultrahigh-resolution proximal segments of these nerves and brachial plexus are of ultrasound (See Case), elastography,21 automation, and the particular interest.15 use of contrast for imaging discrete superficial nerves and

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Case Study: Ultrahigh-Resolution Ultrasound to Diagnose Traumatic Neuropathy

A man, age 50, presented with pain and numbness in the radial sensory nerve action potentials (SNAPs). Evaluation distribution of the superficial radial nerve on the right. His with ultrahigh-resolution ultrasound showed a single fas- symptoms began acutely after a peripheral intravenous cicular enlargement of the right superficial radial nerve at line had been placed in the dorsal wrist. Nerve conduction the symptomatic site consistent with focal nerve trauma studies (NCS) revealed normal and symmetric right and left (Case Figure).

A B C

D

Case Figure. Superficial radial nerve (SRN) distal to site of injury (A) with enlarged, hypoechoic fascicle (B). Distal to the SRN site of injury (C), an injury is also observed that has an enlarged hypoechoic fascicle when viewed longitudinally (D).

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anatomic areas that are difficult to visualize with conven- tional ultrasound. Cranial nerve ultrasound of the optic, facial, vagus, spinal accessory, and hypoglossal nerve is a burgeoning area that may inform both focal pathology and broader NMD such as intracranial hypertension, optic neuritis, Bell’s palsy, Guillain Barré syndrome, CIDP, and CMT.23, 24 n

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Vanessa Baute Penry, MD Associate Professor of Neurology Wake Forest Baptist Medical Center Winston-Salem, NC

Jared Hollinger, MD Neuromuscular Fellow, Neurology Wake Forest Baptist Medical Center Winston-Salem, NC

Disclosures VPB and JH report no financial disclosures.

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