Lisa D. Hobson-Webb

The ultrasonographic wrist-to-forearm median nerve area ratio in carpal tunnel syndrome

OBJECTIVE Peripheral nerve ultrasound is an emerging tool in the diagnosis of carpal tunnel syndrome (CTS). Although numerous publications have cited an increased median nerve area at the wrist to be the diagnostic of CTS, there has been considerable variability in the published normal values for this measurement. Our objective is to collect data on the wrist-to-forearm ratio (WFR) of median nerve area in patients with CTS and healthy controls. METHODS Patients with electrodiagnostically proven CTS underwent ultrasonography of the median nerve at the wrist and forearm. The median nerve area was measured at these points and compared to values from asymptomatic volunteers. RESULTS The WFR of median nerve area in asymptomatic volunteers was 1.0+/-0.1. The WFR in patients presenting with CTS was 2.1+/-0.5. CONCLUSIONS The WFR in patients with CTS is elevated as compared to asymptomatic controls. A WFR of 1.4 gave 100% sensitivity for detecting patients with CTS while using only median nerve area at the wrist resulted in a sensitivity of 45-93%, depending on the cut-off value used. SIGNIFICANCE The WFR of median nerve area promises to be a valid means of diagnosing CTS, and may be superior to measuring median nerve area at the wrist alone.

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

Glycogen Storage Disease Type III diagnosis and management guidelines

Purpose: Glycogen storage disease type III is a rare disease of variable clinical severity affecting primarily the liver, heart, and skeletal muscle. It is caused by deficient activity of glycogen debranching enzyme, which is a key enzyme in glycogen degradation. Glycogen storage disease type III manifests a wide clinical spectrum. Individuals with glycogen storage disease type III present with hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation. Those with type IIIa have symptoms related to liver disease and progressive muscle (cardiac and skeletal) involvement that varies in age of onset, rate of disease progression, and severity. Those with type IIIb primarily have symptoms related to liver disease. This guideline for the management of glycogen storage disease type III was developed as an educational resource for health care providers to facilitate prompt and accurate diagnosis and appropriate management of patients.Methods: An international group of experts in various aspects of glycogen storage disease type III met to review the evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management.Results: This management guideline specifically addresses evaluation and diagnosis across multiple organ systems (cardiovascular, gastrointestinal/nutrition, hepatic, musculoskeletal, and neuromuscular) involved in glycogen storage disease type III. Conditions to consider in a differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, hepatic transplantation, and prenatal diagnosis, are addressed.Conclusions: A guideline that will facilitate the accurate diagnosis and appropriate management of individuals with glycogen storage disease type III was developed. This guideline will help health care providers recognize patients with all forms of glycogen storage disease type III, expedite diagnosis, and minimize stress and negative sequelae from delayed diagnosis and inappropriate management. It will also help identify gaps in scientific knowledge that exist today and suggest future studies.

Median nerve ultrasound as a screening tool in carpal tunnel syndrome: Correlation of cross-sectional area measures with electrodiagnostic abnormality

Introduction: Sonographically measured median nerve cross‐sectional area (CSA) at the wrist is increased in patients with carpal tunnel syndrome (CTS). Ultrasound of the median nerve may be useful in screening for electrodiagnostic (EDx) abnormalities. Methods: EDx studies were performed on all participants. Sonographic evaluation of median nerve CSA at the wrist and in the forearm was performed by a physician blinded to the EDx results. Multivariate and receiver operating characteristic (ROC) analysis were used to assess the data. Results: Fifty control wrists and 192 symptomatic wrists were analyzed. Sensitivity of ultrasound in excluding EDx abnormality was 99% for CSA of 9 mm2 and 97% for a wrist–forearm ratio (WFR) of 1.4. There was no clinically significant correlation between ultrasound parameters and EDx severity. Conclusions: Median nerve ultrasound is a highly sensitive screening tool for EDx abnormality, but it cannot determine severity. This may lead to changes in the current standards for evaluating CTS. Muscle Nerve, 2012

Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of small cell lung cancer

laboratory examinations (erythrocyte sedimentation rate, C-reactive protein, and complete blood count) were otherwise normal. Sonography (Philips iU22 Ultrasound system with a L12-5 50 mm linear transducer) demonstrated a hypoechoic mass of the semitendinosus muscle, which had ill-defined margins. On axial and sagittal images (Fig. 1A,B), the semitendinosus muscle was infiltrated and enlarged. Muscle fibers were thickened, but their orientation was preserved. Doppler examination showed both central and peripheral hypervascularity of the muscle lesion. There was no extension to the adjacent hamstring muscles (biceps femoris or semimembranosus). MR imaging showed focal enlargement of the semitendinosus muscle, with normal signal intensity on T1-weighted images and homogeneous hyperintensity on STIR images. Homogeneous enhancement was observed after intravenous gadolinium administration (Fig. 1C). No other lesions were noted. Swelling and pain disappeared spontaneously within 2 weeks. A follow-up examination performed 4 weeks later showed complete resolution of MR abnormalities (Fig. 1D). The patient made a complete recovery. Long-term follow-up confirmed the final diagnosis of focal myositis. Focal myositis is a rare, benign, soft tissue pseudotumor, which was first described by Heffner et al. Isolated cases have been published, but only 1 study described MRI features in a series of 8 patients. The etiology is unknown. Focal myositis may affect both children and adults. Skeletal muscles of the lower extremities are typically involved, and the most commonly affected site is the thigh. Other locations have been reported. Steroids are commonly used for treatment, but the natural history is for disappearance without treatment. Several authors have described possible recurrence or evolution to polymyositis. The typical appearance on MR imaging is an isointense or slightly hypointense signal on T1-weighted unenhanced images with homogeneous contrast enhancement. Lesions are hyperintense on STIR sequences. MRI may occasionally show the persistence of muscle fiber orientation. The sonographic features of focal myositis have not been described previously. In our patient, sonography showed hypoechoic enlargement of the muscle. Ultrasound can more readily show the thickening of muscle fibers with persistence of fiber orientation better than any other imaging modality. In this patient, there was no history of trauma. Infectious myositis is another cause of myositis, but the clinical and laboratory features were not were not consistent with infection. Other inflammatory processes could be considered, such as proliferative fasciitis, but it was excluded due to the intramuscular location of the lesion. The only other pathology that we considered was polymyositis with focal onset. Because histology cannot differentiate between focal myositis and polymyositis with focal onset, muscle biopsy was not performed. Instead, follow-up examination showed disappearance of abnormalities, and was not consistent with proliferative myositis, polymyositis, or dermatomyositis. In conclusion, we report the sonographic features of focal myositis. In the evaluation of an intramuscular mass, the persistence of fiber orientation can be considered a valuable sign to suggest myositis and rule out a neoplasm. However, one should also consider other inflammatory processes in the differential diagnosis. Long-term follow-up is necessary given the possible evolution to polymyositis, dermatomyositis, or proliferative myositis.

Case-control study of thromboembolic events associated with IV immunoglobulin.

Serious adverse events related to IVIg treatment are unusual, and interventions can be taken to reduce the risk of anaphylaxis, congestive heart failure and renal failure. Stroke and other thromboembolic (TE) events have also been associated with IVIg administration but the risk factors are unknown. This paper investigates whether typical cardiovascular risk factors increase the risk of thromboembolic (TE) events during intravenous immunoglobulin infusion. This case-control study compares 19 patients (mean age = 71 ± 9 years) who experienced a TE event within 2 weeks of IVIg infusion with 38 age-matched controls who received IVIg without experiencing an event. No single cardiovascular risk factor increased the risk of TE event, but the risk was elevated when 2 or more cardiovascular risk factors were present (odds ratio = 1.39, 95 % CI: 0.45, 4.30) and became statistically significant when 4 or more risk factors were present (odds ratio = 10.50, 95 % CI: 1.91, 57.58). The 30 day mortality rate was high in cases (15.8 %) and controls (18.4 %) but not significantly different between the groups.The risk of TE events was increased in individuals with 4 or more cardiovascular risk factors, but, given the wide confidence intervals in our results, the degree of increased risk is difficult to predict. The data suggest that elderly, hospitalized patients receiving IVIg are at moderately elevated risk for TE events and 30 day mortality. Clinicians prescribing IVIg should carefully consider the risk of stroke and myocardial infarction in elderly patients with multiple cardiovascular risk factors, and this risk should be discussed with patients receiving IVIg. Prospective studies of TE events would most accurately demonstrate the incidence and risk factors for these complications.

Autopsy findings in late-onset Pompe disease: A case report and systematic review of the literature

BACKGROUND Late-onset Pompe disease (LOPD) is a rare cause of declining proximal muscle strength and respiratory function that can also affect other organ systems. The development of enzyme replacement therapy has made it one of the few inherited muscle disorders with treatment, but clinical response is difficult to assess due to the variable and often slow progression of illness. A better understanding of the diseases systemic effects can be gleaned through autopsy findings. PURPOSE The purpose of this study was to: (1) describe the histological findings observed in LOPD, (2) provide correlations between reported histological and clinical findings, and (3) review the literature on autopsy findings in LOPD. METHODS Histological evaluation of autopsy tissues from a 62-year-old woman with LOPD was conducted. A clinical history was obtained by review of the medical records. The literature was reviewed for previously reported histological and clinical findings in LOPD. Based on this case report and information from prior publications, histological and clinical findings for the disease were correlated. RESULTS Histologic examination revealed mostly mild vacuolar myopathy typical of glycogen accumulation within skeletal and smooth muscle cells. The most prominent vacuolar myopathy was in quadriceps muscle, which also exhibited chronic myositis with degenerating and regenerating muscle fibers. Transmission electron microscopy disclosed lysosomal glycogen accumulation within skeletal, cardiac, and vascular smooth muscle cells, correlating with published case reports of basilar artery and ascending aortic aneurysms and carotid artery dissection. Organs containing smooth muscle cells (the bladder, intestine, and esophagus) were also affected, explaining reports of symptoms such as urinary incontinence and dysphagia. In addition to glycogen accumulation, there was obvious damage to the contraction apparatus of myofibrils within cardiac and skeletal muscle cells. These histological and ultrastructural findings correlate with the clinical manifestations of LOPD. CONCLUSIONS This study is the first to describe histological findings of LOPD utilizing both traditional paraffin-processed tissues and epoxy resin embedded tissues for high-resolution light microscopy. The findings are similar to those seen in previous studies, but with improved morphological detail and glycogen preservation. This patient exhibited histological involvement of multiple organs, correlating with the clinical features of LOPD. With the advent of definitive therapy for Pompe disease, it is important to be aware of these findings and use them to develop methods for tracking therapeutic response.

Median nerve ultrasonography in carpal tunnel syndrome: Findings from two laboratories

Ultrasonographic (US) enlargement of the median nerve at the wrist is known to be consistent with carpal tunnel syndrome (CTS), although the effects of different measurement techniques, equipment, and patient populations remain unknown. The purpose of this study was to examine the similarities and differences of US findings in CTS between two electromyography (EMG) laboratories. In 2006 and 2007, US measurements of the median nerve were recorded independently and statistically analyzed in patients with CTS at two EMG laboratories (Duke University, Durham, NC, USA, and Università Cattolica del Sacro Cuore, Rome, Italy). Patient age, median nerve area in the forearm, and neurophysiologic score did not differ significantly between the two laboratories. The North Carolina group had a larger median nerve area at the wrist and wrist‐to‐forearm ratio than the Italian group, although both were elevated in reference to established values for the diagnosis of CTS. Median nerve US is less susceptible to differences between laboratories than previously thought, permitting greater generalization of findings. Muscle Nerve 40: 94–97, 2009

Myasthenic syndrome caused by plectinopathy.

Background: Plectin crosslinks intermediate filaments to their targets in different tissues. Defects in plectin cause epidermolysis bullosa simplex (EBS), muscular dystrophy (MD), and sometimes pyloric atresia. Association of EBS with a myasthenic syndrome (MyS) was documented in a single patient in 1999. Objectives: To analyze the clinical, structural, and genetic aspects of a second and fatal case of EBS associated with a MyS and search for the genetic basis of the disease in a previously reported patient with EBS-MD-MyS. Methods: Clinical observations; histochemical, immunocytochemical, and electron microscopy studies of skeletal muscle and neuromuscular junction; and mutation analysis. Results: An African American man had EBS since early infancy, and progressive muscle weakness, hyperCKemia, and myasthenic symptoms refractory to therapy since age 3 years. Eventually he became motionless and died at age 42 years. At age 15 years, he had a marked EMG decrement, and a reduced miniature endplate potential amplitude. The myopathy was associated with dislocated muscle fiber organelles, structurally abnormal nuclei, focal plasmalemmal defects, and focal calcium ingress into muscle fibers. The neuromuscular junctions showed destruction of the junctional folds, and remodeling. Mutation analysis demonstrated a known p.Arg2319X and a novel c.12043dupG mutation in PLEC1. The EBS-MD-MyS patient reported in 1999 also carried c.12043dupG and a novel p.Gln2057X mutation. The novel mutations were absent in 200 Caucasian and 100 African American subjects. Conclusions: The MyS in plectinopathy is attributed to destruction of the junctional folds and the myopathy to defective anchoring of muscle fiber organelles and defects in sarcolemmal integrity.

Carpal tunnel syndrome: clinical features, diagnosis, and management

Carpal tunnel syndrome is the most common peripheral nerve entrapment syndrome worldwide. The clinical symptoms and physical examination findings in patients with this syndrome are recognised widely and various treatments exist, including non-surgical and surgical options. Despite these advantages, there is a paucity of evidence about the best approaches for assessment of carpal tunnel syndrome and to guide treatment decisions. More objective methods for assessment, including electrodiagnostic testing and nerve imaging, provide additional information about the extent of axonal involvement and structural change, but their exact benefit to patients is unknown. Although the best means of integrating clinical, functional, and anatomical information for selecting treatment choices has not yet been identified, patients can be diagnosed quickly and respond well to treatment. The high prevalence of carpal tunnel syndrome, its effects on quality of life, and the cost that disease burden generates to health systems make it important to identify the research priorities that will be resolved in clinical trials.