Muscle ultrasound in neuromuscular disorders

Muscle ultrasound is a useful tool in the diagnosis of neuromuscular disorders, as these disorders result in muscle atrophy and intramuscular fibrosis and fatty infiltration, which can be visualized with ultrasound. Several prospective studies have reported high sensitivities and specificities in the detection of neuromuscular disorders. Although not investigated in large series of patients, different neuromuscular disorders tend to show specific changes on muscle ultrasound, which can be helpful in differential diagnosis. For example, Duchenne muscular dystrophy results in a severe, homogeneous increase of muscle echo intensity with normal muscle thickness, whereas spinal muscular atrophy shows an inhomogeneous increase of echo intensity with severe atrophy. A major advantage of muscle ultrasound, compared to other imaging techniques, is its ability to visualize muscle movements, such as muscle contractions and fasciculations. This study reviews the possibilities and limitations of ultrasound in muscle imaging and its value as a diagnostic tool in neuromuscular disorders.     

Ultrasound of nerve and muscle.

Over the last two decades, ultrasound has developed into a useful technology for the evaluation of diseases of nerve and muscle. Since it is currently not used at by the majority of clinicians involved in diagnosis or care of patients with neuromuscular disorders, this review briefly describes the technical aspects of ultrasound and its physical principles. It relates normal muscle anatomy and movement to ultrasound images in the axial and sagittal planes and follows with a discussion of ultrasound findings in chronic muscle disease. These include evident atrophy and the loss of the hypoechoic architecture of normal muscle tissue. It highlights evolving uses of the technique to measure other pathologic changes in disease including altered muscle dynamics. With high-resolution instruments nerve imaging has now become standard, and the relationships of median nerve anatomy and observations of static and dynamic images from ultrasound are reviewed. Changes seen in carpal tunnel syndrome include significant increases in the cross-sectional area of the nerve just proximal to the site of compression, loss of hyperechoic intensities within nerve, and reduced mobility. Preliminary use of the technique for the study of other nerves is reviewed as well. Ultrasound is an ideal tool for the clinical and research investigation of normal and diseased nerve and muscle complementary to existing diagnostic techniques. As the technology continues to evolve, it will likely assume a more significant role in these areas as those most able to exploit its potential, clinical neurophysiologists and neuromuscular clinicians, incorporate its use at the bedside.     

Computerized real-time neuromuscular sonography: a new application, techniques and methods

Diagnostic ultrasound has been extensively used for neurologic evaluation of cranial, vascular and spinal diseases. This study presents the techniques, methodology, and procedures for a new diagnostic application of ultrasound for evaluation of the neuromuscular system. In order to determine the optimum sonographic characterization of neuromuscular disease, normal anatomy has to be studied with ultrasound to develop a reproducible standardized methodology for routine use of ultrasound in neuromuscular imaging. To fulfill this objective, 30 subjects between the ages of 1 day and 59 years were studied with computerized real-time sonography. The results of this study are presented with illustration of the sonographic images of transverse and longitudinal planes of the upper and lower limbs. Computerization of optimum sonographic techniques, gradation of normal sonographic muscle anatomy by age, and elimination of operator variability were goals that were accomplished, thereby setting the stage for reliable, reproducible muscle imaging by ultrasound.     

Skeletal muscle imaging in neuromuscular disease

Skeletal muscle imaging is increasingly used as a complement to clinical and electrophysiological examination in neuromuscular disease. Ultrasound and MRI have developed as the modalities of choice, each with strengths and limitations. Characteristic changes of muscle denervation and myopathy are seen on imaging which may delineate the nature of the disease process or help guide muscle biopsy. Identifying patterns of muscle involvement in hereditary myopathies may inform genetic testing. This review discusses skeletal muscle imaging in neuromuscular disease focusing on practical applications of current and emerging ultrasound and MRI techniques.     

Ultrasound elastography for the evaluation of peripheral nerves: A systematic review

Peripheral nerve disorders are commonly encountered in clinical practice. Electrodiagnostic studies remain the cornerstone of the evaluation of nerve disorders. More recently, ultrasound has played an increasing complementary role in the neuromuscular clinic. Ultrasound elastography is a technique that measures the elastic properties of tissues. Given the histological changes that occur in diseased peripheral nerves, nerve ultrasound elastography has been explored as a noninvasive way to evaluate changes in nerve tissue composition. Studies to date suggest that nerve stiffness tends to increase in the setting of peripheral neuropathy, regardless of etiology, consistent with loss of more compliant myelin, and replacement with connective tissue. The aim of this systematic review is to summarize the current literature on the use of ultrasound elastography in the evaluation of peripheral neuropathy. Limitations of ultrasound elastography and gaps in current literature are discussed, and prospects for future clinical and research applications are raised.     

Median nerve changes following steroid injection for carpal tunnel syndrome

Introduction: Neuromuscular ultrasound is a painless, radiation‐free, high‐resolution imaging modality for assessment of the peripheral nervous system. The purpose of this study was to use neuromuscular ultrasound to assess the changes that occur in the median nerve after steroid injection for carpal tunnel syndrome (CTS). Methods: Ultrasound and nerve conduction studies were performed at baseline and 1 week, 1 month, and 6 months after steroid injection in 19 individuals (29 wrists) with CTS. Results: Significant changes were noted in median nerve cross‐sectional area (P < 0.001), mobility (P = 0.001), and vascularity (P = 0.042) at the distal wrist crease after steroid injection, and the nerve cross‐sectional area correlated with symptom score and electrodiagnostic parameters. Changes in the ultrasonographic parameters were seen within 1 week of injection. Conclusions: These findings suggest neuromuscular ultrasound is potentially helpful for the assessment of individuals undergoing treatment for CTS, as typical changes can be expected after successful treatment injection. Muscle Nerve 44: 25–29, 2011     

Guidelines for neuromuscular ultrasound training

Neuromuscular ultrasound has become an essential tool in the diagnostic evaluation of various neuromuscular disorders, and, as such, there is growing interest in neuromuscular ultrasound training. Effective training is critical in mastering this modality. Our aim was to develop consensus-based guidelines for neuromuscular ultrasound training courses. A total of 18 experts participated. Expert opinion was sought through the Delphi method using 4 consecutive electronic surveys. A high degree of consensus was achieved with regard to the general structure of neuromuscular ultrasound training; the categorization of training into basic, intermediate, and advanced levels; the learning objectives; and the curriculum for each level. In this study, a group of neuromuscular ultrasound experts established consensus-based guidelines for neuromuscular ultrasound training. These guidelines can be used in the development of the specialty and the standardization of neuromuscular ultrasound training courses and workshops.     

Neuromuscular ultrasound for evaluation of the diaphragm

Neuromuscular clinicians are often asked to evaluate the diaphragm for diagnostic and prognostic purposes. Traditionally, this evaluation is accomplished through history, physical exam, fluoroscopic sniff test, nerve conduction studies, and electromyography (EMG). Nerve conduction studies and EMG in this setting are challenging, uncomfortable, and can cause serious complications, such as pneumothorax. Neuromuscular ultrasound has emerged as a non‐invasive technique that can be used in the structural and functional assessment of the diaphragm. In this study we review different techniques for assessing the diaphragm using neuromuscular ultrasound and the application of these techniques to enhance diagnosis and prognosis by neuromuscular clinicians. Muscle Nerve 47:319‐329, 2013     

Diagnostic ultrasound for nerve transection

The current approach for localizing and assessing the severity of traumatic peripheral nerve injuries involves clinical evaluation and electrodiagnostic studies. However, the ability of this approach to determine the extent of nerve damage within the first 6 weeks after trauma is limited. This is problematic because outcome is improved with early surgical intervention after complete nerve transection. This led us to explore alternative techniques, such as imaging, for assessing peripheral nerve injuries. Twelve fresh cadavers were obtained and after inspection 20 arms were deemed suitable for inclusion in the study. Random sites were transected in median, ulnar, and radial nerves, and sham skin incisions were performed throughout the arm. These nerves were then systematically scanned by an ultrasonographer blinded to the nerve transection sites, who made a final decision as to whether the nerve was transected. High-resolution ultrasound was able to identify transected nerves in the upper extremity with 89% sensitivity and 95% specificity in fresh cadavers. This proof-of-concept study shows that ultrasound can accurately identify nerve transection, which should lead to further ultrasound studies in patients with traumatic peripheral nerve injuries.     

New Keys to Early Diagnosis: Muscle Echogenicity,Nerve Ultrasound Patterns,Electrodiagnostic, and Clinical Parameters in 150 Patients with Hereditary Polyneuropathies

Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry’s disease (n = 7). The CMT1A, followed by the CMT1/4 group, had the most homogeneous enlargement of the nerve cross-sectional areas (CSA) in the ultrasound pattern sum (UPSS) and homogeneity score. Entrapment scores were highest in HNPP, ATTRv amyloidosis, and Fabry’s disease patients. In demyelinating neuropathies, the CSA correlated inversely with nerve conduction studies. The muscle echo intensity was significantly highest in the clinically most affected muscles, which was independent from the underlying disease cause and correlated with muscle strength and disease duration. Further correlations were seen with combined clinical (CMTES-2) and electrophysiological (CMTNS-2) scores of disease severity. We conclude that nerve ultrasound is a helpful tool to distinguish different types of hereditary neuropathies by pattern recognition, whereas muscle ultrasound is an objective parameter for disease severity. The implementation of neuromuscular ultrasound might enrich diagnostic procedures both in clinical routines and research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01141-3.     

Imaging of respiratory muscles in neuromuscular disease: A review

Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease.     

Neuromuscular reaction to paired stimuli

A modification of the twin pulse method is described, by which the nerve tested is stimulated at one proximal site percutaneously and the neuromuscular response to it is derived from a dependent muscle. An electronic subtraction procedure provides separation of the conditioned muscle action potential for measurement by means of a microcomputer. Several parameters were determined in the conditioned action potential and compared to the same criteria in an unconditioned single action potential. Changes of the conditioned action potential were measured at fixed stimulus intervals between 2 and 6 msec. Preliminary normal ranges interindividually and intraindividually were established. Their dependency on skin surface temperature was determined. In polyradiculoneuropathy, the data for motor nerve conduction velocity were characteristically pathologic, and neuromuscular reaction to paired stimuli data deviated minimally from normal. In vincristine neuropathy, motor nerve conduction velocity was normal, but neuromuscular reaction to paired stimuli data fell outside the normal range early in the clinical course. Since polyradiculoneuropathy is a primary demyelinating and remyelinating process and vincristine neuropathy is an example of axonal degeneration, neuromuscular reaction to paired stimuli can facilitate the differential diagnosis in polyneuropathy. Furthermore, this method seems apt to quantify axonal degeneration. In a mixed form of polyneuropathy, peroneal muscular atrophy, motor nerve conduction velocity, as well as neuromuscular reaction to paired stimuli, were abnormal, the latter resulting in abnormally high relative amplitudes. In muscle disorders such as Duchenne muscular dystrophy, neuromuscular reaction to paired stimuli data was abnormal, contrasting experiments using double stimulation of the diseased muscle itself.     

Neuromuscular ultrasound in polyneuropathies and motor neuron disease

Current standards for diagnosing polyneuropathies (PN) and motor neuron disease (MND) sometimes lack early sensitivity and result in delayed diagnosis and treatment. Neuromuscular ultrasound (NMUS), already established in the diagnosis of entrapment neuropathies, may offer another means of diagnosis and monitoring response to therapy. This review of current evidence discusses diffuse nerve hypertrophy in hereditary demyelinating neuropathies, multifocal nerve enlargement in acquired demyelinating PN and the lack of readily apparent structural change in axonal neuropathies. NMUS detection of fasciculations and muscular change in MND is also reviewed, along with the need for further research to better define the role of nerve imaging in patients with PN. Muscle Nerve 47: 790–804, 2013     

AANEM – IFCN glossary of terms in neuromuscular electrodiagnostic medicine and ultrasound

Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide.     

ULTRASOUND IN THE DIAGNOSIS AND MONITORING OF AMYOTROPHIC LATERAL SCLEROSIS: A REVIEW

Neuromuscular ultrasound is complementary to electrodiagnostic (EDx) testing and is useful in enhancing the diagnosis of mononeuropathies, peripheral nerve trauma, and demyelinating polyneuropathies. There is increasing interest in using ultrasound both to aid in the diagnosis of amyotrophic lateral sclerosis (ALS) and to monitor its progression. In this article we review the relevant literature on ultrasound in ALS. Ultrasound is more sensitive than EDx in identifying fasciculations in patients with ALS. It can detect decreased muscle thickness, increased muscle echointensity and echovariance, and reduced peripheral nerve size in these patients. Ultrasound is also a helpful tool in assessment of diaphragm function. Although additional studies are required to define the exact role of ultrasound in the evaluation and monitoring of ALS, it can improve the diagnostic yield in patients when ALS is suspected, but insufficiently supported, by clinical and EDx examinations. Muscle Nerve 60 : 114–123, 2019     

Real‐time visualization of muscle stiffness distribution with ultrasound shear wave imaging during muscle contraction

A stand‐alone ultrasound shear wave imaging technology has been developed to quantify and visualize Young's modulus distribution by remotely applying ultrasound radiation force and tracking the resulting microvibrations in soft tissues with ultrafast ultrasound imaging. We report the first preliminary data that detected the distribution of local muscle stiffness within and between resting and contracting muscles at different muscle lengths with this technology. This technique may assist clinicians in characterizing muscle injuries or neuromuscular disorders. Muscle Nerve, 2010     

Muscle imaging in inherited and acquired muscle diseases

In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders.     

Evidence-based guideline: neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome

Introduction: The purpose of this study was to develop an evidence‐based guideline for the use of neuromuscular ultrasound in the diagnosis of carpal tunnel syndrome (CTS). Methods: Two questions were asked: (1) What is the accuracy of median nerve cross‐sectional area enlargement as measured with ultrasound for the diagnosis of CTS? (2) What added value, if any, does neuromuscular ultrasound provide over electrodiagnostic studies alone for the diagnosis of CTS? A systematic review was performed, and studies were classified according to American Academy of Neurology criteria for rating articles of diagnostic accuracy (question 1) and for screening articles (question 2). Results: Neuromuscular ultrasound measurement of median nerve cross‐sectional area at the wrist is accurate and may be offered as a diagnostic test for CTS (Level A). Neuromuscular ultrasound probably adds value to electrodiagnostic studies when diagnosing CTS and should be considered in screening for structural abnormalities at the wrist in those with CTS (Level B). Muscle Nerve 46: 287–293, 2012     

The diagnosis and management of Piriformis Syndrome: myths and facts

Piriformis Syndrome (PS) is an uncommon, controversial neuromuscular disorder that is presumed to be a compression neuropathy of the sciatic nerve at the level of the piriformis muscle (PM). The diagnosis is hampered by a lack of agreed upon clinical criteria and a lack of definitive investigations such as imaging or electrodiagnostic testing. Treatment has focused on stretching, physical therapies, local injections, including botulinum toxin, and surgical management. This article explores the various sources of controversy surrounding piriformis syndrome including diagnosis, investigation and management. We conclude with a proposal for diagnostic criteria which include signs and symptoms, imaging, and response to therapeutic injections.     

Ultrasound, computed tomography and magnetic resonance imaging in myopathies: correlations with electromyography and histopathology

Imaging of examinations by ultrasound (US), computerized tomography (CT) and low field magnetic resonance imaging (MRI) were compared with EMG and muscle biopsy findings in the same muscles of 33 patients with different neuromuscular diseases. None of the imaging methods revealed specific diagnostic details, but gave valuable information on the extent and distribution of muscle involvement. In myopathies all imaging modalities corresponded well with the EMG and histopathology findings, but in the neuropathies with minimal tissue destruction EMG was, understandably, more sensitive. The imaging characteristics of MR were as good as those of CT, but MRI has the advantage of not requiring ionizing radiation. US is the most economical method and it was found to be, despite its lower resolution, very informative in the hands of an experienced examiner, especially for the detection of fibrosis. The good agreement of histopathology with pathologic imaging and EMG findings implies that the accuracy of muscle biopsy increases, if its site is selected on the basis of imaging and/or EMG examination.