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.

Clinical Utility of Striational Antibodies in Paraneoplastic and Myasthenia Gravis Paraneoplastic Panels.

OBJECTIVE: To critically assess the clinical utility of striational antibodies (StrAbs) within paraneoplastic and myasthenia gravis serological evaluations. METHODS: All Mayo Clinic patients tested for StrAbs from January 1st 2012-December 31st 2018 utilizing Mayo's Unified Data Platform (UDP) were reviewed for neurological diagnosis and cancer. RESULTS: 38,502 unique paraneoplastic and 1,899 MG patients were tested. In paraneoplastic evaluations, the StrAbs positivity rate was higher in cancer vs without cancer (5% [321/6775] vs 4% [1154/31727]; p<0.0001; OR 1.35; CI=1.19-1.53) but ROC analysis indicated no diagnostic accuracy in cancer (AUC=0.505). No neurological phenotype was significantly associated with StrAbs in the paraneoplastic group. Positivity was more common in all MG cancers compared to paraneoplastic cancers (p<0.0001). In MG evaluations, the StrAbs positivity rate was higher in those with cancer vs without (46% [217/474] vs 26% [372/1425]; p<0.0001; OR 2.39, CI 1.9-2.96) with ROC analysis indicating poor diagnostic accuracy for thymic cancer (AUC 0.634, recommended cutoff=1:60, sensitivity=56%, specificity=71%), with worse accuracy for extrathymic cancers (AUC 0.543). In paraneoplastic or MG evaluations, the value of antibody positivity did not improve cancer predictions. Paraneoplastic evaluated patients were more likely with positive StrAbs to obtain computed tomography (CT) (p=0.0001) with 3% (12/468) cancer found. CONCLUSION: Despite a statistically significant association with cancer, an expansive review of performance in clinical service demonstrates that StrAbs are neither specific nor sensitive in predicting malignancy or neurological phenotypes. CT imaging is over utilized with positive StrAbs results. Removal of StrAbs from paraneoplastic or MG evaluations will improve the diagnostic characteristics of the current MG test. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of StrAbs do not accurately identify patients with malignancy or neurological phenotypes.

Transforming the practice of medicine through team science.

BACKGROUND: The translation of biomedical research discoveries into clinical practice is marked by extended timelines (averaging 17 years) and multiple sequential process steps. However, even after a drug, device, diagnostic tool or unique therapeutic procedure successfully navigates through clinical testing to approval, real barriers remain in applying and scaling the innovation in practice. METHODS: Mayo Clinic initiated the Transform the Practice programme to facilitate multidisciplinary team and convergence science to continuously reinvent solutions to address unmet patient needs and accelerate the application of next-generation healthcare solutions. During a 5-year period, 24 programme teams received financial resources, barrier-removing engagement from clinical and research leadership, and enhanced administrative support, including dedicated project managers. RESULTS: The approach created value in facilitating consistent progress toward project objectives and resulted in multiple publications, new extramural funding sources, and implementation of new tests and services into the clinical practice. This report describes the concentrated institutional effort to accelerate the discovery-translation-application continuum in an academic medical centre and highlights successful applications and persistent obstacles. CONCLUSIONS: The Transform the Practice approach is effective in moving high-potential research discoveries closer to implementation in the clinical practice. Its concepts, including the application of structured project management methodology, may be quickly integrated to shorten an organisation's time to implementing its most important discoveries.

The mayo clinic model of clinical integration.

The multi-campus Academic Health Center (AHC) of the future will need to be system-based and committed to clinical integration to continue to meet institutional goals and serve the needs of its patients. The key tactics we describe to accomplish this are.

Compound muscle action potential duration in critical illness neuromyopathy.

INTRODUCTION: We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. METHODS: Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. RESULTS: Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. DISCUSSION: Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018.

Triple Furrowed Atrophic Tongue of Myasthenia Gravis.

The authors present a case and image of a patient with refractory tongue weakness and characteristic triple furrowed pattern of atrophy due to autoimmune myasthenia gravis.

Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia.

OBJECTIVE: To identify the molecular basis of a fatal syndrome of microcephaly, cortical hyperexcitability, and myasthenia. METHODS: We performed clinical and in vitro microelectrode studies of neuromuscular transmission, examined neuromuscular junctions cytochemically and by electron microscopy (EM), and searched for mutations by Sanger and exome sequencing. RESULTS: Neuromuscular transmission was severely compromised by marked depletion of the readily releasable pool of quanta, but the probability of quantal release was normal. Cytochemical and EM studies revealed normal endplate architecture. Exome sequencing identified a homozygous nonsense mutation in the N-terminal domain of MUNC13-1 (UNC13A) truncating the protein after 101 residues. CONCLUSIONS: Loss of Munc13-1 function predicts that syntaxin 1B is consigned to a nonfunctional closed state; this inhibits cholinergic transmission at the neuromuscular junction and glutamatergic transmission in the brain. Inactivation of syntaxin 1B likely accounts for the patient's cortical hyperexcitability because mutations of syntaxin 1B cause febrile seizures with or without epilepsy, haploinsufficiency of the STX1B is associated with myoclonic astatic epilepsy, and antisense knockdown of stx1b in zebrafish larvae elicits epileptiform discharges. A very recent publication also shows that syntaxin 1B has a separate obligatory role for maintenance of developing and mature neurons and illustrates impaired brain development in syntaxin 1A/1B double knockout mice. We therefore attribute our patient's microcephaly to the truncating homozygous Munc13-1 mutation that consigns syntaxin 1B to a permanently closed nonfunctional state akin to a knockout.

Regenerative Medicine Build-Out.

UNLABELLED: Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. SIGNIFICANCE: Regenerative medicine is at the vanguard of health care poised to offer solutions for many of today's incurable diseases. Accordingly, there is a pressing need to develop, deploy, and demonstrate a viable framework for rollout of a regenerative medicine model of care. Translation of regenerative medicine principles into practice is feasible, yet clinical validity and utility must be established to ensure approval and adoption. Standardized and scaled-up regenerative products and services across medical and surgical specialties must in turn achieve a value-added proposition, advancing intended outcome beyond current management strategies.

Regenerative medicine blueprint.

Regenerative medicine, a paragon of future healthcare, holds unprecedented potential in extending the reach of treatment modalities for individuals across diseases and lifespan. Emerging regenerative technologies, focused on structural repair and functional restoration, signal a radical transformation in medical and surgical practice. Regenerative medicine is poised to provide innovative solutions in addressing major unmet needs for patients, ranging from congenital disease and trauma to degenerative conditions. Realization of the regenerative model of care predicates a stringent interdisciplinary paradigm that will drive validated science into standardized clinical options. Designed as a catalyst in advancing rigorous new knowledge on disease causes and cures into informed delivery of quality care, the Mayo Clinic regenerative medicine blueprint offers a patient-centered, team-based strategy that optimizes the discovery-translation-application roadmap for the express purpose of science-supported practice advancement.

Ultrasound applications in electrodiagnosis.

This review article discusses the current scope of high-resolution diagnostic ultrasound in the diagnosis of neuromuscular disease, both as a complementary tool to electrodiagnosis and in some cases as a stand-alone imaging modality. Indications, limitations, potential for research, and training and credentialing are discussed. Indications include needle guidance for nerve conduction studies and needle electromyography, diagnosis of nerve entrapment, diagnostic muscle imaging via grayscale analysis, and dynamic real-time imaging, including sonopalpation, to provide additional diagnostic information. The role of neuromuscular ultrasound in research is discussed, including the need to evaluate the sensitivity, specificity, positive and negative predictive value, and cost-effectiveness of these techniques when they are used alone or in combination. Training and credentialing are reviewed, specifically noting the challenge of the lack of formal training programs and the relatively long, flat learning curve of diagnostic ultrasound.

The Mayo Clinic Value Creation System.

The authors present Mayo Clinic's Value Creation System, a coherent systems engineering approach to delivering a single high-value practice. There are 4 tightly linked, interdependent phases of the system: alignment, discovery, managed diffusion, and measurement. The methodology is described and examples of the results to date are presented. The Value Creation System has been demonstrated to improve the quality of patient care while reducing costs and increasing productivity.

Utility of ultrasound-guided surface electrode placement in lateral femoral cutaneous nerve conduction studies.

INTRODUCTION: Meralgia paresthetica is a common clinical complaint for which some patients ultimately undergo surgical treatment. The lateral femoral cutaneous nerve (LFCN) has been difficult to reliably test electrophysiologically, likely due to anatomic variability and lack of responses in asymptomatic obese subjects. METHODS: We compared a novel ultrasound-guided antidromic sensory nerve conduction study (NCS) with a technique described previously in a population of normal subjects, of whom 50% had body mass indices within the obese range (>27.5). RESULTS: Responses were obtained in at least 92% of subjects using either technique, and 92% of normal subjects had <60% interside variability using the ultrasound-guided technique. CONCLUSIONS: LFCN sensory nerve action potentials can be obtained in the vast majority of normal subjects, even in an obese population and can provide a useful sensory NCS for evaluation of mid-lumbar radiculopathy, plexopathy, or meralgia paresthetica.

Clinical and electrophysiologic features of oculopharyngeal muscular dystrophy: lack of evidence for an associated peripheral neuropathy.

OBJECTIVE: To describe the clinical and electrophysiologic features of an unselected population of patients diagnosed clinically or genetically with oculopharyngeal muscular dystrophy (OPMD), and to discern any association with a peripheral neuropathy. METHODS: Patients with a clinical or genetic diagnosis of OPMD were retrospectively identified and characterized in terms of clinical and electrophysiologic features. RESULTS: Fourteen patients who met the design criteria were identified and included. All had progressive ptosis and dysphagia, and most had ophthalmoparesis and proximal limb weakness. The electromyographic findings were similar to findings in other dystrophic diseases. Nine out of 10 patients had normal sural sensory nerve action potentials (mean amplitude 14.2 muV, range 0-22 muV). CONCLUSIONS: The electrophysiologic findings associated with OPMD are similar to changes noted in other dystrophic diseases. These findings argue against an association between OPMD and peripheral neuropathy. SIGNIFICANCE: OPMD may not be associated with a peripheral neuropathy, as has been previously suggested.

Prolonged compound muscle action potential duration in critical illness myopathy.

Critical illness myopathy (CIM) is a frequent cause of generalized weakness in the intensive care unit. Prolonged compound muscle action potential (CMAP) durations have been described in this patient population, and this study presents further data on CMAP duration in normal controls and patients with CIM. The findings highlight the importance of testing multiple nerve muscle combinations in weak, critically ill patients. Recognition of this pattern, which has not been widely described, can facilitate the diagnosis of CIM.

Electromyographic sensitivity of peroneus tertius relative to abductor hallucis in assessment of peripheral neuropathy.

The objective of this study was to compare the sensitivity of needle electromyography of the abductor hallucis and peroneus tertius muscles in the diagnosis of mild length-dependent peripheral neuropathy (PN). Nerve conduction studies and needle examination were performed on 50 patients with clinical evidence of mild PN. Results demonstrated that the peroneus tertius is as sensitive and is more specific than the abductor hallucis. It is particularly useful when more proximal muscles, such as the tibialis anterior and medial gastrocnemius, are not yet involved.

Ultrasound-guided needle EMG of the diaphragm: technique description and case report.

We describe an ultrasound (US)-guided technique for needle examination of the diaphragm and report a case in which the adjuvant use of diagnostic US in conjunction with electrophysiologic studies provided additional information regarding the motion of the diaphragm in a patient who was a potential candidate for phrenic nerve pacing. US imaging provides excellent direct and real-time visualization of soft tissue, anatomic landmarks, fascial planes, and neurovascular structures. It thereby enhances safety by avoiding accidental needle puncture of vital organs, and it also increases the diagnostic utility of the needle examination.

Urgent surgical decompression compared to methylprednisolone for the treatment of acute spinal cord injury: a randomized prospective study in beagle dogs.

STUDY DESIGN: Experimental dog model of acute spinal cord injury. OBJECTIVE: To compare the relative value of methylprednisolone, surgical decompression, or both for the treatment of traumatic spinal cord injury. SUMMARY OF BACKGROUND DATA: Acute spinal cord injury results from both primary damage to the spinal cord at the time of the initial injury as well as a deleterious secondary cascade of events, which leads to further damage. Surgical decompression is known to improve clinical outcomes, but the timing of surgical decompression remains controversial. METHODS: A nylon tie was used to constrict the spinal cord in 18 adult male beagle dogs. The animals were then prospectively randomized to 3 groups: 1) surgical decompression at 6 hours and intravenous methylprednisolone; 2) surgical decompression at 6 hours and intravenous saline; and 3) intravenous methylprednisolone without surgical decompression. Each animal was evaluated by somatosensory-evoked potentials, daily neurologic assessment, and histologic examination at 2 weeks following injury. RESULTS: Immediately following spinal cord constriction, all animals were paraplegic, incontinent, and the somatosensory-evoked potentials were abolished. Surgical decompression 6 hours after injury, with or without methylprednisolone, led to significantly better neurologic function at 2 weeks than methylprednisolone alone. CONCLUSION: In the setting of acute and persistent spinal cord compression in beagle dogs, surgical decompression 6 hours after injury, with or without methylprednisolone, is more effective for improving neurologic recovery than methylprednisolone alone.

Complications of needle electromyography: hematoma risk and correlation with anticoagulation and antiplatelet therapy.

Electromyography (EMG) is considered a relatively safe procedure based primarily on clinical experience. Literature review reveals few reported complications from bleeding or hematoma formation. No evidence-based guidelines exist for EMG procedures in patients who are taking anticoagulant or antiplatelet medications. The purpose of this study was to determine if patients taking anticoagulant or antiplatelet agents exhibit an increased risk of hematoma formation after routine needle EMG of the tibialis anterior muscle when compared to controls. Study subjects underwent routine needle EMG of the tibialis anterior muscle followed by ultrasound examination to evaluate for the presence of hematoma formation. A mean of 30.8 min elapsed between needle insertion and ultrasound evaluation. A total of 101 patients who were taking warfarin were studied. They had International Normalized Ratio (INR) values at or above 1.5, and two were found to have small, subclinical hematomas. Of 57 patients taking clopidogrel and/or aspirin, 1 was found to have a small, subclinical hematoma. In the control group (51 patients taking neither class of medication), no hematomas were found on ultrasound. This study suggests that hematoma formation from a standard needle EMG is rare. In addition, hematoma formation in our study group of patients on anticoagulant or antiplatelet medications was also uncommon, and no patients with documented hematomas experienced symptoms. These findings should be considered when determining the feasibility of electrodiagnostic evaluation of patients who are taking anticoagulant or antiplatelet medications.