pinecone/core-2020-05-10-deduplication huggingface dataset:
Inverse correlation between VEGF and soluble VEGF receptor 2 in POEMS with AIDP responsive to intravenous immunoglobulin

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-band, and skin changes) syndrome is characterized by chronic progressive polyneuropathy and plasma-cell dyscrasia. A major diagnostic criterion of POEMS is elevation of circulating vascular endothelial growth factor (VEGF), which is believed to play a pathogenic role in this disease. We report a case of POEMS that presented as relapsing acute inflammatory demyelinating polyneuropathy, in which complete remission after intravenous immunoglobulin (IVIg) treatment was unexpectedly observed. At clinical nadir, the VEGF level was 30-fold higher, and the soluble form of VEGF receptor 2 (sVEGFR2), which acts as a decoy for VEGF, was 2.7-fold lower than normal. These changes combined might contribute to the pathogenesis of POEMS, inducing vascular permeability and tissue edema. At 9-month follow-up, during clinical remission, VEGF and sVEGFR2 were near normal values. sVEGFR2 reduction is a new finding in POEMS. IVIg treatment may benefit POEMS patients with acute neuropathy by downgrading VEGF release induced by inflammatory cytokines
Rippling is not always electrically silent in rippling muscle disease.

Rippling muscle disease (RMD) is a myopathy with hyperirritability, the pathophysiology for which is uncertain.We report electromyographic findings in a 30-year-old man with RMD. Clinical features included muscle rippling and percussion-induced rapid muscle contractions. Both were associated with bursts of short-duration, low-amplitude spikes, which resembled single muscle fiber discharges. Our case stands in contrast to previously reported cases, which showed either electrical silence or motor unit potential discharges associated with rippling, and may represent muscle fiber hyperexcitability
Dominant and Recessive RYR1 Mutations in Adults with Core Lesions and Mild Muscle Symptoms

INTRODUCTION: Ryanodine receptor gene (RYR1) mutations have been associated with central core disease (CCD), multiminicore/minicore/multicore disease (MmD), and susceptibility to malignant hyperthermia (MH).
METHODS: Patients with muscle symptoms in adulthood, who had features compatible with CCD/MmD, underwent clinical, histological, and genetic (RYR1 and SEPN1 genes) evaluations. Published cases of CCD and MmD with adult onset were also reviewed.
RESULTS: Eight patients fulfilled the criteria for further analysis. Five RYR1 mutations, 4 of them unreported, were detected in 3 patients. Compound heterozygosity was proven in 1 case.
CONCLUSIONS: To our knowledge, this is the only report of adult onset associated with recessive RYR1 mutations and central core/multiminicores on muscle biopsy. Although adult patients with CCD, MmD, and minimally symptomatic MH with abnormal muscle biopsy findings usually have a mild clinical course, differential diagnosis and carrier screening is crucial for prevention of potentially life-threatening reactions to general anesthesia
Questionnaire tools for the diagnosis of carpal tunnel syndrome from the patient history

Introduction: There remains no “gold standard” for the diagnosis of carpal tunnel syndrome (CTS). Clinical diagnosis is often held to be paramount but depends on the skills of the individual practitioner. We describe two mathematical approaches to the analysis of a history obtained by questionnaire. Methods: We used two earlier instruments, a conventional logistic regression analysis, and an artificial neural network to analyze data from 5860 patients referred for diagnosis of hand symptoms. We evaluated their ability to predict whether nerve conduction studies would show evidence of CTS using receiver operating characteristic curves. Results: Both new instruments outperformed the existing tools, achieving sensitivity of 88% and specificity of 50% in predicting abnormal median nerve conduction. When combined, 96% sensitivity and 50% specificity were achieved. Conclusion: The combined instrument can be used as a preliminary screening tool for CTS, for self-diagnosis, and as a supplement to diagnosis in primary care
Transforming growth factor‐beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin‐1 and scleraxis

Introduction:  Transforming growth factor‐beta (TGF‐β) is a well‐known regulator of fibrosis and inflammation in many tissues. During embryonic development, TGF‐β signaling induces expression of the transcription factor scleraxis, which promotes fibroblast proliferation and collagen synthesis in tendons. In skeletal muscle, TGF‐β has been shown to induce atrophy and fibrosis, but the effect of TGF‐β on muscle contractility and the expression of scleraxis and atrogin‐1, an important regulator of muscle atrophy, were not known.  Methods:  We treated muscles from mice with TGF‐β and measured force production, scleraxis, procollagen Iα2, and atrogin‐1 protein levels.  Results:  TGF‐β decreased muscle fiber size and dramatically reduced maximum isometric force production. TGF‐β also induced scleraxis expression in muscle fibroblasts, and increased procollagen Iα2 and atrogin‐1 levels in muscles.  Conclusion:  These results provide new insight into the effect of TGF‐β on muscle contractility and the molecular mechanisms behind TGF‐β–mediated muscle atrophy and fibrosis. Muscle Nerve 45: 55–59, 201
Differential aging of median and ulnar sensory nerve parameters

Introduction:  Nerve conduction velocity slows and amplitude declines with aging.  Methods:  Median and ulnar sensory nerves were tested at the annual meetings of the American Dental Association. Seven hundred four subjects had at least two observations. The rate of change in the nerve parameters was estimated while controlling for gender, age, change in hand temperature, baseline body mass index (BMI), and change in BMI.  Results:  Amplitudes of the median sensory nerve action potentials decreased by 0.58 μV per year, whereas conduction velocity decreased at a rate of 0.41 m/s per year. Corresponding values for the ulnar nerve were 0.89 μV and 0.29 m/s per year. The rates of change in amplitudes did not differ, but the median nerve demonstrated a more rapid loss of conduction velocity.  Conclusions:  The rate of change for the median conduction velocity was higher than previously reported. The rate of change of median conduction velocity was significantly greater than for the ulnar nerve. Muscle Nerve 45: 60–64, 201
Frontal plane hip and ankle sensorimotor function, not age, predicts unipedal stance time

Introduction:  Changes occur in muscles and nerves with aging. In this study we explore the relationship between unipedal stance time (UST) and frontal plane hip and ankle sensorimotor function in subjects with diabetic neuropathy.  Methods:  UST, quantitative measures of frontal plane ankle proprioceptive thresholds, and ankle and hip motor function were tested in 41 subjects with a spectrum of lower limb sensorimotor function ranging from healthy to moderately severe diabetic neuropathy.  Results:  Frontal plane hip and ankle sensorimotor function demonstrated significant relationships with UST. Multivariate analysis identified only composite hip strength, ankle proprioceptive threshold, and age to be significant predictors of UST ( R  2  = 0.73), explaining 46%, 24%, and 3% of the variance, respectively.  Conclusions:  Frontal plane hip strength was the single best predictor of UST and appeared to compensate for less precise ankle proprioceptive thresholds. This finding is clinically relevant given the possibility of strengthening the hip, even in patients with significant peripheral neuropathy. Muscle Nerve, 201
Agreement between clinical screening procedures for neuropathy in the feet

Introduction:  The correlation between monofilament testing, symptom surveys, and electrodiagnostic studies for the diagnosis of axonal polyneuropathy has not been well studied. This investigation was done to assess the agreement between these procedures in a non‐random sample of volunteers.  Methods:  The procedures evaluated included electrodiagnostic tests of the sural nerve, monofilament testing of the great toe, a symptom survey, and a body diagram. Kappa coefficients and sensitivity and specificity, using nerve conduction as a “gold standard,” were used to determine the agreement between various combinations of procedures.  Results:  Poor agreement (kappa values −0.12–0.44) and sensitivity (sensitivity <30%) were found for all combinations of symptoms and monofilament results in comparison with sural peak latency and amplitude.  Conclusions:  Overall, the results demonstrated a low discriminatory power for the screening procedures for identifying persons with impaired sural nerve function. The results highlight the need for further development and evaluation of screening methods for distal neuropathy in population‐based studies. Muscle Nerve, 201
The risk of hematoma following extensive electromyography of the lumbar paraspinal muscles

Introduction:  The purpose of this study is to provide a controlled trial looking at the risk of paraspinal hematoma formation following extensive paraspinal muscle electromyography.  Methods:  54 subjects ages 55–80 underwent MRI of the lumbar spine before or shortly after electromyography using the paraspinal mapping technique. A neuroradiologist, blinded to the temporal relationship between the EMG and MRI, reviewed the MRIs to look for hematomas in or around the paraspinal muscles.  Results:  Two MRIs demonstrated definite paraspinal hematomas, while 10 were found to have possible hematomas. All hematomas were < 15 mm, and none were close to any neural structures. There was no relationship between MRI evidence of hematoma and either the timing of the EMG or the use of aspirin or other nonsteroidal anti‐inflammatory drugs.  Conclusions:  Paraspinal electromyography can be considered safe in the general population and those taking nonsteroidal anti‐inflammatory drugs. Muscle Nerve 46:26–30, 201
Muscle x-ray attenuation is not decreased during experimental bed rest.

Muscle X-ray attenuation (MXA) in\ud
Hounsfield units (HU) is decreased in dystrophy, aging, and\ud
immobilization. We hypothesized a decrease also during bed\ud
rest (BR). Methods: Twenty-five healthy men performed BR for\ud
90 days, 8 of whom performed flywheel exercise 2–3 times per\ud
week. Muscle cross-sectional area (CSA) and MXA were\ud
assessed by computed tomography. Results: In the control\ud
group, calf muscle CSA decreased during 89-day BR by 26.6\ud
(SD 3.8) %, while MXA increased by 1.2 HU on day 28 and\ud
almost reached baseline values on day 89. Changes were mitigated\ud
in the flywheel group for the calf (P < 0.001). All changes\ud
were reversed within 90 days after BR. Conclusions: Results\ud
contradict the initial hypothesis. Increased intramuscular blood\ud
content, interstitial fluid space shrinkage, and reduction of intramuscular\ud
lipid stores are possible explanations for the moderate\ud
increase in MXA during the initial phase of bed rest
Optical inhibition of motor nerve and muscle activity

Introduction: There is no therapeutic approach that provides precise and rapidly reversible inhibition of motor nerve and muscle activity for treatment of spastic hypertonia. Methods: We used optogenetics to demonstrate precise and rapidly reversible light-mediated inhibition of motor nerve and muscle activity in vivo in transgenic Thy1::eNpHR2.0 mice. Results: We found optical inhibition of motor nerve and muscle activity to be effective at all muscle force amplitudes and determined that muscle activity can be modulated by changing light pulse duration and light power density. Conclusions: This demonstration of optical inhibition of motor nerves is an important advancement toward novel optogenetics-based therapies for spastic hypertonia.Stanford University (Stanford Bio-X Interdisciplinary Initiatives Award)Stanford University (National Institutes of Health Graduate Training Program in Biotechnology grant)W. M. Keck Foundation (grant)National Institutes of Health (U.S.) (NIH grant R01NS080954
Re‐analysis of an original   CMTX3   family using exome sequencing identifies a known   BSCL2   mutation

Introduction  Charcot–Marie–Tooth ( CMT ) disease is a group of peripheral neuropathies affecting both motor and sensory nerves.  CMTX3  is an X‐linked  CMT  locus, which maps to chromosome  Xq26 .3–q27.3. Initially,  CMTX3  was mapped to a 31.2‐Mb region in 2 American families. We have reexamined 1 of the original families ( US‐PED2 ) by next generation sequencing.    Methods  Three members of the family underwent exome sequencing. Candidate variants were validated by  PCR  and Sanger sequencing analysis.    Conclusion  No pathogenic coding variants localizing to the  CMTX3  region were identified. However, exome sequencing identified a known   BSCL2   mutation ( N88S ). This study demonstrates the power of exome sequencing as a tool to identify gene mutations for a small family in the absence of statistically significant linkage data. Muscle Nerve 47: 922–924, 201
Symmetry of paraspinal muscle denervation in clinical lumbar spinal stenosis: Support for a hypothesis of posterior primary ramus stretching?

Introduction  Denervation of the paraspinal muscles in spinal disorders is frequently attributed to radiculopathy. Therefore, patients with lumbar spinal stenosis causing asymmetrical symptoms should have asymmetrical paraspinal denervation.    Methods  Seventy‐three patients with clinical lumbar spinal stenosis, aged 55–85 years, completed a pain drawing and underwent masked electrodiagnostic testing, including bilateral paraspinal mapping and testing of 6 muscles on the most symptomatic (or randomly chosen) limb.    Results  With the exception of 10 subjects with unilateral thigh pain ( P  = 0.043), there was no relationship between side of pain and paraspinal mapping score for any subgroups (symmetrical pain, pain into 1 calf only). Among those with positive limb  EMG  (tested on 1 side), no relationship between side of pain and paraspinal EMG score was found.    Conclusion  Evidence suggests that paraspinal denervation in spinal stenosis may not be due to radiculopathy, but rather due to stretch or damage to the posterior primary ramus.  Muscle Nerve , 48: 198–203, 201
A trial of proficiency of nerve conduction: Greater standardization still needed

Introduction  The aim of this study was to test the proficiency (accuracy among evaluators) of measured attributes of nerve conduction (NC).    Methods  Expert clinical neurophysiologists, without instruction or consensus development, from 4 different medical centers, independently assessed 8 attributes of NC in 24 patients with diabetes mellitus (DM) on consecutive days.    Results  No significant intraobserver differences between days 1 and 2 were found, but significant interobserver differences were seen. Use of standard reference values did not correct for these observed differences.    Conclusions  Interobserver variability was attributed to differences in performance of NC. It was of sufficient magnitude that it is of concern for the conduct of therapeutic trials. To deal with interrater variability in therapeutic trials, the same electromyographers should perform all NC assessments of individual patients or, preferably, NC procedures should be more standardized. A further trial is needed to test whether such standardization would eliminate interobserver variability.  Muscle Nerve   48 : 369–374, 201
Electromyography‐related pain: Muscle selection is the key modifiable study characteristic

Introduction : The aim of this study was to estimate the effects of patient, provider, and study characteristics on electromyography (EMG)‐related pain.  Methods : Patients undergoing EMG rated their EMG‐related pain after each muscle was studied on a 100‐point visual analog scale (VAS). Investigators recorded the order in which the muscles were sampled, the total time spent with the needle in each muscle, and whether electrical endplate noise was noted.  Results : A total of 1781 muscles were studied in 304 patients. Eleven muscles were associated with significantly more or less pain than the others. Endplate noise was associated with more pain (5.4 mm, 95% CI 2.8–7.0). There was a small, but significant effect from needling time (0.02 mm, 95% CI 0.00–0.04).  Conclusions : Among factors that electromyographers can control, muscle selection has the greatest impact on pain. Our data include an extensive list of muscle‐specific EMG‐related pain scores. Provider and other study characteristics have little or no impact on EMG‐related pain. Muscle Nerve 49:570–574, 201
Multicenter trial of the proficiency of smart quantitative sensation tests

Introduction : We assessed proficiency (accuracy and intra‐ and intertest reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic sensorimotor polyneuropathy (DSPN).  Methods : Technologists from 3 medical centers using different but identical QSTs independently assessed 6 modalities of sensation of the foot (or leg) twice in patients without ( n  = 6) and with ( n  = 6) DSPN using smart computer assisted QSTs.  Results : Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intraclass correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra‐ or intertest differences were observed.  Conclusions : These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra‐ or intertest differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length‐dependent sensorimotor polyneuropathies.  Muscle Nerve   49 : 645–653, 201
Proficiency of nerve conduction using standard methods and reference values (cl. NPhys Trial 4)

Introduction  The Cl. NPhys Trial 3 showed that attributes of nerve conduction (NC) were without significant intraobserver differences, although there were significant interobserver differences.  Methods : Trial 4 tested whether use of written instructions and pretrial agreement on techniques and use of standard reference values, diagnostic percentile values, or broader categorization of abnormality could reduce significant interobserver disagreement and improve agreement among clinical neurophysiologists.  Results : The Trial 4 modifications markedly decreased, but did not eliminate, significant interobserver differences of measured attributes of NC. Use of standard reference values and defined percentile values of abnormality decreased interobserver disagreement and improved agreement of judgment of abnormality among evaluators. Therefore, the same clinical neurophysiologist should perform repeat NCs of therapeutic trial patients.  Conclusions : Differences in interobserver judgment of abnormality decrease with use of common standard reference values and a defined percentile level of abnormality, providing a rationale for their use in therapeutic trials and medical practice.  Muscle Nerve  50: 900–908, 201
Chloride channels in myotonia congenita assessed by velocity recovery cycles

Introduction: Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. Methods: MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched normal controls. Results: MC patients exhibited increased early supernormality, but treatment with sodium channel blockers prevented this. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. Discussion: MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that in dominant MC the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve. © 2013 Wiley Periodicals, Inc
Hip strength: Ankle proprioceptive threshold ratio predicts falls and injury in diabetic neuropathy

Introduction : We determined lower limb neuromuscular capacities associated with falls and fall‐related injuries in older people with declining peripheral nerve function.  Methods : Thirty‐two subjects (67.4 ± 13.4 years; 19 with type 2 diabetes), representing a spectrum of peripheral neurologic function, were evaluated with frontal plane proprioceptive thresholds at the ankle, frontal plane motor function at the ankle and hip, and prospective follow‐up for 1 year.  Results : Falls and fall‐related injuries were reported by 20 (62.5%) and 14 (43.8%) subjects, respectively. The ratio of hip adductor rate of torque development to ankle proprioceptive threshold (Hip STR /Ank PRO ) predicted falls (pseudo‐R 2  = .726) and injury (pseudo‐R 2  = .382). No other variable maintained significance in the presence of Hip STR /Ank PRO .  Conclusions : Fall and injury risk in the population studied is related inversely to Hip STR /Ank PRO . Increasing rapidly available hip strength in patients with neuropathic ankle sensory impairment may decrease risk of falls and related injuries.  Muscle Nerve   50 : 437–442, 201
Patient perception of pain versus observed pain behavior during a standardized electrodiagnostic test

Introduction: Clinicians often assume that observations of pain behavior are adequate for assessment of patient pain perception during procedures. This has not been tested during a standardized electrodiagnostic experience. Methods: During a prospective trial including extensive, standardized electrodiagnostic testing on persons with lumbar stenosis, vascular claudication, and asymptomatic volunteers, the subjects and an observer rated levels of pain. Results: In 60 subjects, observers significantly under‐rated pain (Visual Analog Scale 3.17 ± 2.23 vs. 4.38 ± 2.01, t = −4.577, df = 59, P < 0.001). Perceived pain during testing related to bodily pain as measured by the visual analog, McGill, Pain Disability, and Quebec scales, but not age, duration of symptoms, Tampa kinesiphobia, Center for Epidemiological Studies Depression scale, or SF‐36 health quality of life. Conclusions: Persons with worse pain syndromes may perceive more pain during testing than others. Clinicians and researchers should understand that patients may have more pain than they recognize. Muscle Nerve 51: 185–191, 201
Ultrasonographic identification of nerve pathology in neuralgic amyotrophy: Enlargement, constriction, fascicular entwinement and torsion.

Objective: To characterize the ultrasonographic findings on nerves in neuralgic amyotrophy. Methods: Fourteen patients with neuralgic amyotrophy were examined using high resolution ultrasound. Results: Four types of abnormalities were found: 1. Focal or diffuse nerve / fascicle enlargement (57%), 2. incomplete nerve constriction (36%), 3. complete nerve constriction with torsion (50%) (hourglass-like appearance), and 4. fascicular entwinement (28%). Torsions were confirmed intraoperatively and occurred on the radial nerve in 85% of the patients. A significant correlation was found between no spontaneous recovery of  nerve function and constriction / torsion / fascicular entwinement (p=0.007). Conclusion: Ultrasonographic nerve pathology in neuralgic amyotrophy varies in order of severity from nerve enlargement to constriction to nerve torsion, with treatment moving from conservative to surgical. We postulate that the constriction caused by inflammation is the precursor of torsion and that the development of nerve torsion is facilitated by rotational movements of limbs. This article is protected by copyright. All rights reserved