Rotational 3D shear wave elasticity imaging: Effect of knee flexion on 3D shear wave propagation in in vivo vastus lateralis.

Skeletal muscle is a complex tissue, exhibiting not only direction-dependent material properties (commonly modeled as a transversely isotropic material), but also changes in observed material properties due to factors such as contraction and passive stretch. In this work, we evaluated the effect of muscle passive stretch on shear wave propagation along and across the muscle fibers using a rotational 3D shear wave elasticity imaging system and automatic analysis methods. We imaged the vastus lateralis of 10 healthy volunteers, modulating passive stretch by imaging at 8 different knee flexion angles (controlled by a BioDex system). In addition to demonstrating the ability of this acquisition and automatic processing system to estimate muscle shear moduli over a range of values, we evaluated potential higher order biomarkers for muscle health that capture the change in muscle stiffness along and across the fibers with changing knee flexion. The median within-subject variability of these biomarkers is found to be <16%, suggesting promise as a repeatable clinical metric. Additionally, we report an unexpected observation: that shear wave signal amplitude along the fibers increases with increasing flexion and muscle stiffness, which is not predicted by transversely isotropic (TI) material simulations. This observation may point to an additional potential biomarker for muscle health or inform other material modeling choices for muscle.

Pregnancy in MuSK-positive myasthenia gravis: A single-center case series.

INTRODUCTION/AIMS: Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. Our objective in this study was to describe the course of MMG during pregnancy and within 6 months postpartum, and to document any effect on fetal health. METHODS: A retrospective review was performed of medical records of patients with MMG seen in the Duke Myasthenia Gravis Clinic from 2003 to 2022. MMG patients with onset of MMG symptoms before or during pregnancy as well as within 6 months postpartum were reviewed. RESULTS: A total of 14 pregnancies in 10 patients were included in our study cohort. Initial MG symptoms developed during pregnancy or within 6 months postpartum in six patients. Four patients had two pregnancies, three of whom developed MG during their first pregnancy. In the patients diagnosed before pregnancy, MG symptoms increased in five of eight patients during pregnancy or postpartum. Four patients required rescue therapy with plasma exchange or intravenous immunoglobulin during pregnancy or postpartum. One patient had a cesarean section after prolonged labor due to failure of progression. There were no other complications of pregnancy or delivery, and all infants were healthy at delivery. DISCUSSION: As in non-MuSK MG, women with MMG may also have worsening or may develop initial MG symptoms during pregnancy or within 6 months postpartum. More aggressive medical therapy may be required for pregnant patients with MMG. Further study is needed to identify the mechanism and risk of worsening of MMG during pregnancy or postpartum.

Neuromuscular ultrasound standardized scanning techniques and protocols: Expert panel recommendations.

Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular disorders at many centers. Despite its growing utility, uniform standard scanning techniques do not currently exist. Scanning approaches for similar diseases vary in the literature creating heterogeneity in the studies as reported in several meta-analysis. Moreover, neuromuscular ultrasound experts including the group in this study have different views with regards to technical aspects, scanning protocols, and the parameters that should be assessed. Establishing standardized neuromuscular scanning protocols is essential for the development of the subspeciality to ensure uniform clinical and research practices. Therefore, we aimed to recommend consensus-based standardized scanning techniques and protocols for common neuromuscular disorders using the Delphi approach. A panel of 17 experts participated in the study, which consisted of three consecutive electronic surveys. The first survey included voting on six scanning protocols addressing the general scanning technique and five common categories of suspected neuromuscular disorders. The subsequent surveys focused on refining the protocols and voting on new steps, rephrased statements, or areas of non-agreement. A high degree of consensus was achieved on the general neuromuscular ultrasound scanning technique and the scanning protocols for focal mononeuropathies, brachial plexopathies, polyneuropathies, amyotophic lateral sclerosis, and muscle diseases. In this study, a group of neuromuscular ultrasound experts developed six consensus-based neuromuscular ultrasound scanning protocols that may serve as references for clinicians and researchers. The standardized protocols could also aid in achieving high-quality uniform neuromuscular ultrasound practices.

The Duke Myasthenia Gravis Clinic Registry: II. Analysis of outcomes.

INTRODUCTION/AIMS: The Duke Myasthenia Gravis (MG) Clinic Registry contains comprehensive physician-derived data on patients with MG seen in the Duke MG Clinic since 1980. The aim of this study was to report outcomes in patients seen in the clinic and treated according to the International Consensus Guidance statements. METHODS: This is a retrospective cohort study of patients initially seen after 2000 and followed for at least 2 years in the clinic. Treatment goal (TG) was defined as achieving MGFA post-intervention status of "minimal manifestations" or better; PIS was determined by the treating neurologist. Time-to-event analysis, including Cox proportional hazards modeling, was performed to assess the effect of sex, acetylcholine receptor antibody (AChR-Ab) status, age at disease onset, distribution (ocular vs generalized), thymectomy, and thymoma on the time to achieve TG. RESULTS: Among the 367 cohort patients, 72% achieved TG (median time less than 2 years). A greater proportion of patients with AChR-Abs and thymectomy achieved TG and they did so sooner than patients without these antibodies or thymectomy. Otherwise, there were no significant differences in these findings within the tested subgroups. The disease duration at the first Duke Clinic visit was shorter in patients who achieved TG than in those who did not. DISCUSSION: These results demonstrate outcomes that can be achieved in patients with MG treated according to the current Consensus Guidance statements. Among other things, they can be used to determine the added value and potential role of new treatment modalities developed since 2018.

Carpal tunnel syndrome: updated evidence and new questions.

Carpal tunnel syndrome is the most common entrapment neuropathy, affecting quality of life for many people. Although it is a well recognised condition, new insights into epidemiology, diagnosis, and treatment have emerged in the past 6 years. The availability of disease-modifying treatments for rare systemic disorders associated with carpal tunnel syndrome (eg, amyloidosis) should alert clinicians to these diagnostic possibilities. Besides clinical evaluation and electrophysiology, the role of ultrasonography as a diagnostic tool has been confirmed and new ultrasound techniques have been applied, the clinical use and feasibility of which require further investigation. Surgical and non-surgical interventions are beneficial for the treatment of carpal tunnel syndrome and several treatment options are now available, giving clinicians the possibility to choose the best approach for every patient. New diagnostic and therapeutic techniques require further validation.

Repeatability of Rotational 3-D Shear Wave Elasticity Imaging Measurements in Skeletal Muscle.

Shear wave elasticity imaging (SWEI) usually assumes an isotropic material; however, skeletal muscle is typically modeled as a transversely isotropic material with independent shear wave speeds in the directions along and across the muscle fibers. To capture these direction-dependent properties, we implemented a rotational 3-D SWEI system that measures the shear wave speed both along and across the fibers in a single 3-D acquisition, with automatic detection of the muscle fiber orientation. We tested and examined the repeatability of this system's measurements in the vastus lateralis of 10 healthy volunteers. The average coefficient of variation of the measurements from this 3-D SWEI system was 5.3% along the fibers and 8.1% across the fibers. When compared with estimated respective 2-D SWEI values of 16.0% and 83.4%, these results suggest using 3-D SWEI has the potential to improve the precision of SWEI measurements in muscle. Additionally, we observed no significant difference in shear wave speed between the dominant and non-dominant legs along (p = 0.26) or across (p = 0.65) the muscle fibers.

Ultrasound-guided-electromyography in plegic muscle: Usefulness of nerve stimulation.

INTRODUCTION/AIMS: In traumatic nerve lesions (TNLs), motor unit potentials (MUPs) may be difficult to detect in early injury. Ultrasound-guided electromyography (US-EMG) can aid in identifying areas of muscle activation, but its sensitivity can be improved. In this study we compare the sensitivity of US-EMG alone with US-EMG after peripheral nerve stimulation (NC-US-EMG) to better identify active muscle regions. METHODS: In this prospective study, 32 patients with severe TNLs were evaluated with standard EMG (ST-EMG), US-EMG, and NC-US-EMG at baseline (T0), after 2 to 3 months (T1), and after 5 to 6 months (T2). RESULTS: NC-US-EMG was more sensitive in detecting MUPs compared with US-EMG and ST-EMG at T0 (19 patients vs 14 and 5 patients, respectively). In addition, both US-guided techniques were more sensitive than ST-EMG in detecting MUPs (ST-EMG vs US-EMG: P = .014; ST-EMG vs NC-US-EMG: P = .003). At T1, ST-EMG remained less sensitive NC-US-EMG (P = .019). No significant differences were observed among the three techniques at T2. DISCUSSION: In the evaluation of severe TNLs, the combination of peripheral nerve stimulation and US increases the sensitivity of EMG for MUP detection at baseline and 2 to 3 months postinjury.

Classical Complement Pathway Inhibition in a "Human-On-A-Chip" Model of Autoimmune Demyelinating Neuropathies.

Chronic autoimmune demyelinating neuropathies are a group of rare neuromuscular disorders with complex, poorly characterized etiology. Here we describe a phenotypic, human-on-a-chip (HoaC) electrical conduction model of two rare autoimmune demyelinating neuropathies, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), and explore the efficacy of TNT005, a monoclonal antibody inhibitor of the classical complement pathway. Patient sera was shown to contain anti-GM1 IgM and IgG antibodies capable of binding to human primary Schwann cells and induced pluripotent stem cell derived motoneurons. Patient autoantibody binding was sufficient to activate the classical complement pathway resulting in detection of C3b and C5b-9 deposits. A HoaC model, using a microelectrode array with directed axonal outgrowth over the electrodes treated with patient sera, exhibited reductions in motoneuron action potential frequency and conduction velocity. TNT005 rescued the serum-induced complement deposition and functional deficits while treatment with an isotype control antibody had no rescue effect. These data indicate that complement activation by CIDP and MMN patient serum is sufficient to mimic neurophysiological features of each disease and that complement inhibition with TNT005 was sufficient to rescue these pathological effects and provide efficacy data included in an investigational new drug application, demonstrating the model's translational potential.

A scoping review of methods used in musculoskeletal soft tissue and nerve shear wave elastography studies.

This scoping review of shear wave elastography (SWE) articles in musculoskeletal soft tissue and nerve research demonstrates methodological heterogeneity resulting from a lack of standardized data collection and reporting requirements. Seven literature databases were searched for original articles published in English from 2004-2020 that examine human skeletal muscles, tendons, and nerves in vivo. Although 5,868 records were initially identified, only 375 reports met inclusion criteria. Of the 375 articles, 260 examined 89 unique muscles, 94 examined 14 unique tendons, and 43 examined 8 unique nerves. Cohorts were often small (n = 11-20) and young (mean = 20-29 years), and participants were typically tested in the prone position. Regarding equipment, a variety of ultrasound systems (n = 11), ultrasound models (n = 18), and transducers (n = 19) were identified. Only 11% of articles contained information on the use of electromyography to confirm absence of muscle activity, and only 8% reported measurement depth. Since musculoskeletal soft tissue and nerve stiffness can vary significantly based on data collection methods, it is essential to standardize SWE collection and reporting procedures. This will allow SWE to serve as a valid and reproducible tool for assessing tissue pathology, disease progression, and response to intervention within a variety of musculoskeletal and nerve-related disorders.

Expert consensus on the combined investigation of carpal tunnel syndrome with electrodiagnostic tests and neuromuscular ultrasound.

Expert consensus was sought to guide clinicians on the use of electrodiagnostic tests (EDX) and neuromuscular ultrasound (NMUS) in the investigation of suspected carpal tunnel syndrome (CTS). Consensus was achieved using the Delphi method via three consecutive anonymised surveys of 15 experts and was defined as rating agreement ≥ 80%. The panel agreed that combining EDX and NMUS is more informative than using each modality alone. NMUS adds value in patients with clinically suspected CTS with non-localizing or normal EDX, atypical EDX, failed CTS surgery, polyneuropathy, and CTS suspected to be secondary to structural pathology. The median nerve cross-sectional area should be measured at the site of maximal nerve enlargement, and the nerve should be scanned from mid-forearm to the palm. The group also identified those situations where the wrist-to-forearm area ratio and longitudinal scans of the median nerve should also be obtained. EDX should always be performed to quantify CTS severity and in individuals over age 70. This document is an initial step to guide clinicians on the combined investigation of CTS using EDX and NMUS, to be updated regularly with the emergence of new research.

Full Characterization of in vivo Muscle as an Elastic, Incompressible, Transversely Isotropic Material Using Ultrasonic Rotational 3D Shear Wave Elasticity Imaging.

Using a 3D rotational shear wave elasticity imaging (SWEI) setup, 3D shear wave data were acquired in the vastus lateralis of a healthy volunteer. The innate tilt between the transducer face and the muscle fibers results in the excitation of multiple shear wave modes, allowing for more complete characterization of muscle as an elastic, incompressible, transversely isotropic (ITI) material. The ability to measure both the shear vertical (SV) and shear horizontal (SH) wave speed allows for measurement of three independent parameters needed for full ITI material characterization: the longitudinal shear modulus µL , the transverse shear modulus µT , and the tensile anisotropy χE . Herein we develop and validate methodology to estimate these parameters and measure them in vivo, with µL = 5.77±1.00 kPa, µT = 1.93±0.41 kPa (giving shear anisotropy χµ = 2.11±0.92 ), and χE = 4.67±1.40 in a relaxed vastus lateralis muscle. We also demonstrate that 3D SWEI can be used to more accurately characterize muscle mechanical properties as compared to 2D SWEI.

Quantitative muscle ultrasound and electrical impedance myography in late onset Pompe disease: A pilot study of reliability, longitudinal change and correlation with function.

BACKGROUND/OBJECTIVES: Late-onset Pompe disease (LOPD) is slowly progressive, making it difficult to assess clinical change and response to interventions. In this study, quantitative muscle ultrasonography (QMUS) and electrical impedance myography (EIM) were evaluated as potential biomarkers. METHODS: 25 patients with confirmed LOPD were recruited from the Duke Pompe Clinic and evaluated with standard clinical measures, QMUS, standard EIM (sEIM) and hand-held EIM (hEIM). Patients were evaluated at baseline, 12 months and 24 months. MUS, sEIM and hEIM were compared with the clinical data. Five patients were given hEIM devices to perform measurements at home. RESULTS: QMUS and hEIM had good reliability as measures of muscle structure and conduction properties. Home, patient-performed hEIM measurements did not differ significantly from those performed in the clinic setting. Thirteen patients completed all follow-up measures. Most measures did not change over the study period, however, vastus lateralis echointensity increased 27%, a sign of declining muscle health. Additionally, significant correlations between QMUS, hEIM and measures of muscle strength and function were present. CONCLUSIONS: QMUS and hEIM may provide useful outcome measures for future studies in LOPD with hEIM providing an opportunity to collect data at home. Larger, multicenter studies are needed to explore these possibilities.

Expert consensus on the combined investigation of ulnar neuropathy at the elbow using electrodiagnostic tests and nerve ultrasound.

The addition of ultrasound (US) to electrodiagnostic (EDX) tests can significantly enhance the accuracy of testing for ulnar neuropathy at the elbow (UNE). We aimed to obtain expert consensus to guide clinicians on the combined use of EDX and US in UNE investigation. Consensus was achieved using the Delphi method. Two consecutive anonymised questionnaires were submitted to 15 experts, who were asked to choose their level of agreement with each statement. Consensus was pre-defined as ≥ 80% rating agreement. The experts concluded that all investigations of UNE should include both nerve conduction studies and US. There was consensus that US should include cross-sectional area measurement and assessment of nerve mobility at the elbow, and that the entire ulnar nerve should be imaged. This study defined expert opinion on the 'core' techniques that should be used routinely in the UNE investigation using EDX and US. Areas with lack of consensus highlighted some controversial issues in the current use of these diagnostic modalities and the need for future research. This document is an initial step to guide clinicians on the combined investigation of UNE using EDX and US, to be regularly updated as new research emerges.

Tongue weakness and atrophy differentiates late-onset Pompe disease from other forms of acquired/hereditary myopathy.

Late-onset Pompe disease (LOPD) is an inherited autosomal recessive progressive metabolic myopathy that presents in the first year of life to adulthood. Clinical presentation is heterogeneous, differential diagnosis is challenging, and diagnostic delay is common. One challenge to differential diagnosis is the overlap of clinical features with those encountered in other forms of acquired/hereditary myopathy. Tongue weakness and imaging abnormalities are increasingly recognized in LOPD. In order to explore the diagnostic potential of tongue involvement in LOPD, we assessed tongue structure and function in 70 subjects, including 10 with LOPD naive to treatment, 30 with other acquired/hereditary myopathy, and 30 controls with neuropathy. Tongue strength was assessed with both manual and quantitative muscle testing. Ultrasound (US) was used to assess tongue overall appearance, echointensity, and thickness. Differences in tongue strength, qualitative appearance, echointensity, and thickness between LOPD subjects and neuropathic controls were statistically significant. Greater tongue involvement was observed in LOPD subjects compared to those with other acquired/hereditary myopathies, based on statistically significant decreases in quantitative tongue strength and sonographic muscle thickness. These findings provide additional evidence for tongue involvement in LOPD characterized by weakness and sonographic abnormalities suggestive of fibrofatty replacement and atrophy. Findings of quantitative tongue weakness and/or atrophy may aid differentiation of LOPD from other acquired/hereditary myopathies. Additionally, our experiences in this study reveal US to be an effective, efficient imaging modality to allow quantitative assessment of the lingual musculature at the point of care.

The Role of Imaging for Disorders of Peripheral Nerve.

Peripheral nerve imaging is a helpful and sometimes essential adjunct to clinical history, physical examination, and electrodiagnostic studies. Advances in imaging technology have allowed the visualization of nerve structures and their surrounding tissues. The clinical applications of ultrasound and magnetic resonance imaging (MRI) in the evaluation of peripheral nerve disorders are growing exponentially. This article reviews basics of ultrasound and MRI as they relate to nerve imaging, reviews advantages and limitations of each imaging modality, reviews the applications of ultrasound and MRI in disorders of peripheral nerve, and discusses emerging advances in the field.

The Duke myasthenia gravis clinic registry: I. Description and demographics.

INTRODUCTION: The Duke Myasthenia Gravis (MG) Clinic Registry is a disease-specific database containing physician-derived data from patients seen in the Duke MG Clinic since 1980. METHODS: Data from 1060 MG patients initially seen between 1980 and 2008 were reviewed. RESULTS: Fifty-four percent were male. Symptoms began after age 50 in 66% of males and 42% of females. Peak onset age in males was in their 60's; females had no predominant onset age. Onset age for both sexes increased from 1980 to 2008. Thymoma was present in 8.5%. Weakness was limited to ocular muscles for at least 2 y in 22% and became generalized later in 8.3% of these. Acetylcholine receptor antibodies were present in 78% overall, 82% with generalized MG and 52% with ocular MG (OMG). The distribution of MG disease class was similar in males and females, except that a greater proportion of women experienced myasthenic crisis and men were more likely to have OMG. DISCUSSION: Data in the Registry permit comprehensive and longitudinal analysis of a validated MG population. Analysis of Registry data shows that the frequency of AChR antibody negative MG, ocular MG, and thymoma are similar to other reports, but the onset age and proportion of males have progressively increased compared to studies published more than 20 y ago. These observations demonstrate the value of collecting comprehensive clinical information and comparing historic and contemporary populations. Other potential uses of Registry data include comparison of outcome measures in different disease subgroups and the response to specific treatments.