Paradoxical thinning of the diaphragm on ultrasound is a risk factor for requiring non-invasive ventilation in patients with neuromuscular diaphragmatic dysfunction.

INTRODUCTION/AIMS: Point-of-care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with neuromuscular diaphragmatic dysfunction, paradoxical thinning of the diaphragm during inspiration is observed on ultrasound; however, its frequency, electrodiagnostic associations, and prognostic significance remain uncertain. METHODS: Medical records of patients presenting to two electrodiagnostic laboratories (Mayo Clinic, Rochester, Minnesota and University of Alberta, Edmonton, Alberta) from January 1, 2022 to December 31, 2022, for evaluation of suspected neuromuscular respiratory failure, were reviewed. RESULTS: 214 patients were referred and 19 patients excluded due to incomplete information. Of 195 patients (384 hemidiaphragms), 104 had phrenic neuropathy, 12 had myopathy, and 79 had no evidence of neuromuscular disease affecting the diaphragm. Paradoxical thinning occurred in 31 (27%) patients with neuromuscular diaphragmatic dysfunction and was unilateral in 30, the majority (83%) having normal contralateral ultrasound. Phrenic nerve conduction studies and diaphragm electromyography results did not distinguish patients with paradoxical thinning versus without. Most patients (71%) with paradoxical thinning required non-invasive ventilation (NIV), including 16 with unilateral paradoxical thinning. Paradoxical thinning and BMI ≥30 kg/m2 were risk factors for requiring NIV in multivariable logistic regression analysis, with odds ratios of 2.887 (95% CI:1.166, 7.151) and 2.561 (95% CI: 1.186, 5.532), respectively. DISCUSSION: Paradoxical thinning of the diaphragm occurs in patients with prominent neuromuscular diaphragmatic dysfunction, most commonly from phrenic neuropathy, and is a significant risk factor for requiring NIV. Unilateral paradoxical thinning is sufficient for needing NIV. BMI ≥30 kg/m2 additionally increases risk of requiring NIV in patients with neuromuscular diaphragmatic dysfunction.

Compound Muscle Action Potential and Myosin-Loss Pathology in Patients With Critical Illness Myopathy: Correlation and Prognostication.

BACKGROUND AND OBJECTIVES: Prolonged compound muscle action potential (CMAP) duration and preferential loss of myosin are considered the diagnostic hallmarks of critical illness myopathy (CIM); however, their correlation and prognostic values have not been studied. We aimed to investigate the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss. METHODS: We searched the Mayo Clinic Electromyography Laboratory databases (1986-2021) for patients diagnosed with CIM on the basis of prolonged distal CMAP durations (>15 msec in fibular motor nerve studies recording over the tibialis anterior or >8 msec in other motor nerves) and needle EMG findings compatible with myopathy. Electrodiagnostic studies were generally performed within 24 hours after weakness became noticeable. We included only patients who underwent muscle biopsy. Clinical, electrophysiologic, and myopathologic data were reviewed. We conducted myosin/actin ratio analysis when muscle tissue was available. We used the Fisher exact test for categorical data comparisons and the Mann-Whitney 2-tailed test for continuous data. We applied the Kaplan-Meier technique to analyze survival rates. RESULTS: Twenty patients (13 female patients) were identified [median age at diagnosis of 62.5 years (range: 19-80 years)]. The median onset of weakness was 24 days (range: 1-128) from the first day of intensive care unit admission. Muscle biopsy showed myosin loss in 14 patients, 9 of whom had >50% of myofibers affected (high grade). Type 2 fiber atrophy was observed in 19 patients, 13 of whom also had myosin loss. Patients with myosin loss had higher frequency of steroid exposure (14 vs 3; p = 0.004); higher median number of necrotic fibers per low-power field (2.5 vs 1, p = 0.04); and longer median CMAP duration (msec) of fibular (13.4 vs 8.75, p = 0.02), tibial (10 vs 7.8, p = 0.01), and ulnar (11.1 vs 7.95, p = 0.002) nerves compared with those without. Only patients with high-grade myosin loss had reduced myosin/actin ratios (<1.7). Ten patients died during median follow-up of 3 months. The mortality rate was similar between patients with and without myosin loss. Patients with high-grade myosin loss had a lower overall survival rate than those with low-grade or no myosin loss, but this was not statistically significant (p = 0.05). DISCUSSION: Myosin loss occurred in 70% of the patients with CIM with prolonged CMAP duration. Longer CMAP duration predicts myosin-loss pathology. The extent of myosin loss marginally correlates with the mortality rate. Our findings highlight the potential prognostic values of CMAP duration and myosin loss severity in predicting disease outcome.

Parsonage-Turner Syndrome and Hereditary Brachial Plexus Neuropathy.

Parsonage-Turner syndrome and hereditary brachial plexus neuropathy (HBPN) present with indistinguishable attacks of rapid-onset severe shoulder and arm pain, disabling weakness, and early muscle atrophy. Their combined incidence ranges from 3 to 100 in 100,000 persons per year. Dominant mutations of SEPT9 are the only known mutations responsible for HBPN. Parsonage and Turner termed the disorder "brachial neuralgic amyotrophy," highlighting neuropathic pain and muscle atrophy. Modern electrodiagnostic and imaging testing assists the diagnosis in distinction from mimicking disorders. Shoulder and upper limb nerves outside the brachial plexus are commonly affected including the phrenic nerve where diaphragm ultrasound improves diagnosis. Magnetic resonance imaging can show multifocal T2 nerve and muscle hyperintensities with nerve hourglass swellings and constrictions identifiable also by ultrasound. An inflammatory immune component is suggested by nerve biopsies and associated infectious, immunization, trauma, surgery, and childbirth triggers. High-dose pulsed steroids assist initial pain control; however, weakness and subsequent pain are not clearly responsive to steroids and instead benefit from time, physical therapy, and non-narcotic pain medications. Recurrent attacks in HBPN are common and prophylactic steroids or intravenous immunoglobulin may reduce surgical- or childbirth-induced attacks. Rehabilitation focusing on restoring functional scapular mechanics, energy conservation, contracture prevention, and pain management are critical. Lifetime residual pain and weakness are rare with most making dramatic functional recovery. Tendon transfers can be used when recovery does not occur after 18 months. Early neurolysis and nerve grafts are controversial. This review provides an update including new diagnostic tools, new associations, and new interventions crossing multiple medical disciplines.

Electrodiagnostic and ultrasound evaluation of respiratory weakness.

Phrenic nerve conduction studies (NCSs) and needle electromyography (EMG) can provide important information on the underlying pathophysiology in patients presenting with unexplained shortness of breath, failure to wean from the ventilator, or consideration of phrenic nerve pacemaker implantation. However, these techniques are often technically challenging, require experience, can lack sensitivity and specificity, and, in the case of diaphragm EMG, involve some degree of risk. Diagnostic high-resolution ultrasound has been introduced in recent years as an adjuvant technique readily available at the bedside that can increase the overall sensitivity and specificity of the neurophysiologic evaluation of respiratory symptoms. Two-dimensional ultrasound in the zone of apposition can identify atrophy and evaluate contractility of the diaphragm, in addition to localizing a safe zone for needle EMG. M-mode ultrasound can identify decreased excursion or paradoxical motion of the diaphragm and can increase the reliability of phrenic NCSs. When used in combination, ultrasound, phrenic NCSs and EMG of the diaphragm can differentiate neuropathic, myopathic, and central disorders, and can offer aid in prognosis that is difficult to arrive at solely from clinical examination. This article will review techniques to successfully perform phrenic NCSs, needle EMG of the diaphragm, and ultrasound of the diaphragm. The discussion will include technical pitfalls and clinical pearls as well as future directions and clinical indications.

Distal Tibial Mononeuropathy From Compression by the Posterior Tibial Artery: Clinical-Electrophysiological-Ultrasonographic Correlations.

SUMMARY: The tibial nerve is bound tightly to the posterior tibial artery in the tarsal tunnel where expansion capacity is limited. Therefore, the nerve may be vulnerable to, and damaged by chronic pulsatile trauma from an atypically positioned overriding artery, labeled "punched-nerve syndrome". In this article, we present a 49-year-old woman who presented with two months of severe burning pain in the left medial ankle and sole of the foot without antecedent trauma. Neurological examination identified dysesthetic sensation to light touch in the left medial sole of the foot, and both active and passive dorsiflexion worsened the painful paresthesia. Nerve conduction studies demonstrated a reduced left medial plantar mixed nerve action potential amplitude, 50% less than the right. High-resolution ultrasound (HRUS) showed an increased left tibial nerve cross-sectional area of 26 mm2 (normal <22.3 mm2) at the level of the ankle with side-to-side difference of 6 mm2 (normal <5.7 mm2). The distal tibial nerve and its medial plantar branch were atypically positioned immediately deep to the left posterior tibial artery and abnormally flattened with focal enlargement of the nerve on longitudinal view. Dynamic analysis demonstrated the nerve being compressed with each pulsation of the tibial artery immediately above. Active dorsiflexion of the ankle narrowed the space underneath the flexor retinaculum resulting in further compression of the nerve against the artery. In conclusion, HRUS as an adjunct to electrophysiological studies identified punched-nerve arterial compression as an etiology of tarsal tunnel syndrome.

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.

A standardized ultrasound approach in neuralgic amyotrophy.

Neuralgic amyotrophy (NA), also referred to as idiopathic brachial plexitis and Parsonage-Turner syndrome, is a peripheral nerve disorder characterized by acute severe shoulder pain followed by progressive upper limb weakness and muscle atrophy. While NA is incompletely understood and often difficult to diagnose, early recognition may prevent unnecessary tests and interventions and, in some situations, allow for prompt treatment, which can potentially minimize adverse long-term sequalae. High-resolution ultrasound (HRUS) has become a valuable tool in the diagnosis and evaluation of NA. Pathologic HRUS findings can be grouped into four categories: nerve swelling, swelling with incomplete constriction, swelling with complete constriction, and fascicular entwinement, which may represent a continuum of pathologic processes. Certain ultrasound findings may help predict the likelihood of spontaneous recovery with conservative management versus the need for surgical intervention. We recommend relying heavily on history and physical examination to determine which nerves are clinically affected and should therefore be assessed by HRUS. The nerves most frequently affected by NA are the suprascapular, long thoracic, median and anterior interosseous nerve (AIN) branch, radial and posterior interosseous nerve (PIN) branch, axillary, spinal accessory, and musculocutaneous. When distal upper limb nerves are affected (AIN, PIN, superficial radial nerve), the lesion is almost always located in their respective fascicles within the parent nerve, proximal to its branching point. The purpose of this review is to describe a reproducible, standardized, ultrasonographic approach for evaluating suspected NA, and to share reliable techniques and clinical considerations when imaging commonly affected nerves.

Utility of Carpal Tunnel Release and Ulnar Decompression in CMT1A and HNPP.

INTRODUCTION/AIMS: Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure-palsies (HNPP) and Charcot-Marie-Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. METHODS: Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression. RESULTS: CTS occurred in 53.3% of HNPP and 11.5% of CMT1A, while CuTS was present in 43.3% of HNPP and 5.8% of CMT1A patients. CTS decompression occurred in 10-HNPP and 5-CMT1A patients, and CuTS decompression with/without transposition was performed in 5-HNPP and 1-CMT1A patients. In HNPP, electrodiagnostic studies identified median neuropathy at the wrist in 9/10 patients and ultrasound showed focal enlargements at the carpal and cubital tunnels. In CMT1A, median and ulnar sensory responses were all absent, and the nerves were diffusely enlarged. After CTS surgery, pain, sensory loss, and strength improved in 4/5 CMT1A, and 6/10 HNPP patients. Of clinical, electrophysiologic and ultrasound findings, only activity-provoked features significantly correlated with CTS surgical benefit in HNPP patients (odds ratio = 117.0:95% confidence interval, 1.94 > 999.99, p = 0.01). One CMT1A and one HNPP patient improved with CuTS surgery while 2 HNPP patients worsened. DISCUSSION: CTS symptom improvement post-surgery can be seen in CMT1A and (less frequent) in HNPP patients. CuTS surgery commonly worsened course in HNPP. Activity-provoked symptoms in HNPP best informed benefits from CTS surgery.

Efficacy and Tolerability of Topical Platelet Exosomes for Skin Rejuvenation: Six-Week Results.

BACKGROUND: Exosomes are regenerative mediators for skin rejuvenation. Human platelet extract (HPE) is an allogeneic exosome product derived from US-sourced, leukocyte-reduced apheresed platelets with consistent purity and potency. OBJECTIVES: The authors sought to better characterize the safety and tolerability of novel HPE (plated) Intensive Repair Serum (Rion Aesthetics, Rochester, MN) and its maximal effects on skin rejuvenation at 6 weeks. METHODS: This prospective, single-arm, non-randomized, longitudinal study investigated the safety and efficacy of HPE. Structured sub-analysis evaluated multifactorial improvement in skin health following standardized skin care regimen to determine the maximal effect. Evaluation at baseline and 6 weeks included participant questionnaires and photo documentation with VISIA-CR Generation 5 3D PRIMOS (Canfield Scientific Inc, Fairfield, NJ). RESULTS: VISIA-CR imaging yielded quantifiable and statistically significant improvements in overall skin health (skin health score). A greater score correlated to greater overall skin health, and there was a statistically significant mean delta improvement of 224.2 ± 112.8 (mean ± standard deviation, P ≤ 0.0001) in skin health score at 6 weeks compared with baseline. This correlated to reduction in redness, wrinkles, and melanin production across all cosmetic units (P = 0.005, P = 0.0023, P ≤ 0.0001, respectively) and significant improvements in luminosity and color evenness (P ≤ 0.001). CONCLUSIONS: A topically applied platelet-derived exosome product, HPE, induced normalization to skin health at 4 to 6 weeks with improved various clinical measures of facial photodamage and cutaneous aging. It is safe, well-tolerated, and well-liked by participants.

Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 21 consecutive severe post-COVID-19 survivors admitted to an inpatient rehabilitation hospital, 16 (76%) of them had at least one sonographic abnormality of diaphragm muscle structure or function. This corresponded to a significant reduction in diaphragm muscle contractility as represented by thickening ratio (muscle thickness at maximal inspiration/end-expiration) for the post-COVID-19 compared to non-COVID-19 cohorts. These findings may shed new light on neuromuscular respiratory dysfunction as a contributor to prolonged functional impairments after hospitalization for post-COVID-19.

Diagnostic accuracy of gray scale muscle ultrasound screening for pediatric neuromuscular disease.

OBJECTIVE: Gray scale ultrasound (US) has been demonstrated to be a sensitive and specific tool in the diagnosis of pediatric neuromuscular disease (NMD). With recent advances in genetic testing, the diagnostic work up for NMD has evolved. The purpose of this study was to compare the current diagnostic value of gray scale US to previously defined sensitivities and specificities to determine when this test can add value to a patient's diagnostic workup. METHODS: Standardized quantitative gray scale US imaging was performed on 148 pediatric patients presenting for electrodiagnostic testing to evaluate for NMD. Patients were categorized as having an NMD, a non-NMD, or as "uncertain." The US results were defined as normal, borderline or abnormal based on echointensity values. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the test were calculated. RESULTS: Forty-five percent of the patients had an NMD, 54% a non-NMD, and in 1% the diagnosis remained uncertain. US was abnormal in 73% of myopathies, 63% of neuromuscular junction disorders, 60% of generalized neuropathies and 58% of focal neuropathies. After excluding patients in whom muscle US was not expected to be abnormal (eg, sensory neuropathy), sensitivity was 83%, specificity 79%, PPV 75%, NPV 86%, and accuracy 81%. CONCLUSIONS: Quantitative gray scale muscle US still has good diagnostic value as a screening tool in pediatric NMD. As with any diagnostic test, muscle US is best used in conjunction with history and physical examination to increase specificity and diagnostic yield.

Neuromuscular ultrasound competency assessment: Consensus-based survey.

Neuromuscular ultrasound is a rapidly evolving specialty with direct application for patient care. Competency assessment is an essential standard needed to ensure quality for practitioners, particularly for those newly acquiring skills with the technique. Our aim was to survey experts' opinions regarding physician competency assessment of neuromuscular ultrasound and to identify minimal competency of knowledge and skills. The opinions of 18 experts were obtained through the Delphi method using two consecutive electronic surveys. A high degree of consensus was achieved on items regarding framework and the conduct of neuromuscular ultrasound assessment and the knowledge and skills that a candidate needs to attain minimal competency in neuromuscular ultrasound. In this study, a group of neuromuscular ultrasound experts developed a general framework for neuromuscular ultrasound competency assessment and recommended testable areas of knowledge and skills suitable for establishing minimal competency.

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.

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. HIGHLIGHTS: Optimal terminology in neuromuscular electrodiagnosis and ultrasound has been revisited. A team of international experts have revised and expanded a standardized glossary. This list of terms serves as standard reference for clinical practice, education and research.

Improved Treatment Response Following Magnetic Resonance Imaging-Guided Focused Ultrasound for Lumbar Facet Joint Pain.

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a noninvasive modality that allows for precise tissue ablation with sparing of surrounding structures. Early reports of the use of MRgFUS for the treatment of facet joint osteoarthritis are promising. We present a case of facet joint pain treated successfully by MRgFUS at our institution. Magnetic resonance imaging-guided focused ultrasonography may be a useful modality for patients with facet joint-mediated low back pain, particularly in the setting of limited or refractory response to conventional treatments.

Phrenic neuropathy water immersion dyspnea: Clinical findings and need for patient counseling.

OBJECTIVE: To investigate the following among patients with phrenic neuropathy: (1) occurrences of water immersion activity-induced dyspnea; (2) clinical, electrophysiologic, sonographic, and pulmonary function test abnormalities; and (3) frequency of documented counseling regarding the risks of water immersion activities. METHODS: We identified all patients with test-confirmed phrenic neuropathy seen from January 1, 2000, to December 31, 2018, at Mayo Clinic. RESULTS: Of 535 patients with phrenic neuropathy, documentation of dyspnea with water activities was identified in 4% (22/535). The risks of water immersion were only documented in patients having experienced this problem. The majority had isolated phrenic neuritis or neuralgic amyotrophy syndrome (77.3%), mean age was 55 years (range 31-79), and most patients were men (81.9%). Patients had right-sided (45.5%) or bilateral (54.5%) phrenic neuropathy. None had isolated left phrenic involvement. Near-fatal drowning occurred in 18.2% (4/22), with persons needing assistance to be rescued from the water, following diving into water. Dyspnea with water immersion was the only symptom in 4.5% (1/22) and the presenting respiratory symptom in 36.4% (8/22). A range of electrophysiologic, sonographic, and pulmonary function test abnormalities including mild abnormalities were seen and not found to be significantly different from those in patients in whom water-induced dyspnea was not recorded. CONCLUSION: Respiratory distress with water immersion activities is a serious complication of phrenic neuropathies. Physician-documented counseling is lacking. Isolated phrenic neuritis, neuralgic amyotrophy, and right-sided and bilateral phrenic involvement are most commonly implicated, but the range of severity and testing abnormalities suggest that all patients with neuralgic amyotrophy or phrenic neuropathy should be warned especially about diving into water.

Establishing Normal Values for F-Wave Latencies in Diagnosing Peripheral Neuropathies for the Pediatric Population.

PURPOSE: We present a unique technique applying F-wave latencies to assist in the diagnosis of peripheral neuropathy within the pediatric age group. METHODS: We calculated an F-wave estimated deviance adjusted for limb length measurements, distal motor conduction velocity, and distal motor latencies. We compared the F-wave estimated deviance from the normal subjects with those with peripheral neuropathy (both axonal and demyelinating) to establish diagnostic accuracy in pediatric patients. RESULTS: The normal range for the F-wave estimated deviance in the upper limb was -1 to +6 ms and in the lower limb was -8 to +5 ms. When compared with 82 subjects with peripheral neuropathy, there was a significant difference between the normal subjects and those with neuropathy (P values between 0.002 and 0.0005 for each of the individual nerves tested). CONCLUSIONS: The F-wave estimated deviance is independent of age and can be accurately applied to the electrodiagnostic testing of pediatric patients with suspected neuropathy.