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PurposeThis study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS).MethodsIn this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively.ResultsA model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p ConclusionsIn people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism.Implications for rehabilitationMultiple sclerosis (MS) affects people of working age, significantly interfering with work productivity.Higher cognitive and physical impact of fatigue were associated with more presenteeism in workers with MS.A higher cognitive impact of fatigue and more depressive symptoms were associated with absenteeism in workers with MS.Occupational and healthcare professionals should be aware of the impact of both physical and mental health on work productivity in workers with MS.

BackgroundA healthy diet has been associated with less symptoms or progression of disease in multiple sclerosis (MS). However, whether specific diets are needed, or general healthy diet recommendations are sufficient is unknown.ObjectiveTo investigate the association between diet quality, use of diets, and quality of life (QoL) in men and women with MS.MethodsDiet quality was measured with the Dutch Healthy Diet-index, which measures adherence to the Dutch Guidelines for a Healthy Diet. QoL was assessed with the MSQoL-54 questionnaire. A total of 728 people were included (623 women, 105 men). Multiple linear regression, stratified for gender, was used to analyse the data.ResultsIn women with MS, an association was found between diet quality and both physical and mental QoL after adjusting for several confounders (Physical Health Composite Score (beta=0.410; P=0.001); Mental Health Composite Score (beta=0.462; P=0.002)). Similar results were less pronounced in men. Subjects following a specific diet had higher diet quality and QoL than subjects not following a diet.ConclusionAdherence to the Dutch dietary guidelines is associated with better physical and mental QoL, especially in women. Following an MS-specific diet may help to adhere to these guidelines.

Nerve ultrasound scanning has become a valuable diagnostic tool in the routine workup of peripheral nerve disorders, effectively complementing conventional electrodiagnostic studies. The most relevant sonographic features are nerve size and structural integrity. Several peripheral neuropathies show characteristic and distinct patterns of nerve enlargement, allowing their early and accurate identification, and reducing test-burden and diagnostic delay for patients. In mononeuropathies such as carpal tunnel syndrome and ulnar neuropathy at the elbow, nerve enlargement develops only at specific sites of entrapment, while in polyneuropathy the nerve enlargement may be multifocal, regional or even diffuse. Nerve ultrasound scanning can reliably identify chronic inflammatory neuropathies, even when extensive electrodiagnostic studies fail, and it should therefore be embedded in routine diagnostic workup of peripheral neuropathies. In this paper we describe a potential diagnostic strategy to achieve this.

Carpal tunnel syndrome is a common peripheral nerve entrapment neuropathy caused due to compression of the median nerve at the level of the wrist joint. Bifid median nerve associated with a persistent median artery is a rare entity and in itself asymptomatic anatomical variant. However, distension of the persistent median artery due to a thrombus can be symptomatic due to compression on the median nerve and can compromise the blood flow to the palm. We report a case of persistent median artery thrombosis in a young female patient who presented with symptoms of carpal tunnel syndrome diagnosed on the ultrasonography and confirmed on the MRI with subsequent improvement post anticoagulation therapy.

Summary Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (≥12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of ≥6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7–9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. This study is registered with the Netherlands Trial Register, NTR 2224/NL2107. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1·4 (95% CI 0·6–3·3; p=0·45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13–24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products.

Objective: The gold standard for diagnosis of giant cell arteritis (GCA) is a temporal artery biopsy (TAB). We sought for a clinical useful model to predict when an invasive TAB is not necessary to confirm GCA. Methods: A prospective cohort study was conducted with patients > 50 years with possible GCA, presenting with newly onset headache and/or visual loss. Demographical, clinical, laboratory findings and histological data were collected. Results: Fifty-six (70%) of the 94 patients showed 1 or more halos of the superficial temporal artery branches. Ultrasound-guided biopsy was positive in 28 patients (30%). Four independent variables predicted a positive TAB: weight loss, bilateral headache, positive halo sign and thrombocytosis. The ROC of the model had an area under the curve of 0.932 with a PPV of 83% and a NPV of 94%. Conclusions: Weight loss, bilateral headache, a positive halo sign with duplex and thrombocytosis are the most important clinical and laboratory predictors for GCA in a selected group of patients. Significance: In patients > 50 years presenting with new onset headache or visual loss with 3 or more of the above mentioned risk factors, a biopsy of the temporal artery is not needed to confirm the diagnosis GCA.KEY MESSAGES In our study biopsy of the temporal artery was positive in 30% of the patients with possible GCA Weight loss, bilateral headache, a positive halo sign on duplex and thrombocytosis are predictors for GCA The halo sign had a high sensitivity but a low specificity for a biopsy proven GCA.

Chronic obstructive and pulmonary disease (COPD) has detrimental effects on individuals with the disease. COPD causes breathlessness, morbidity and associated psychosocial distress. This study was guided by the phenomenological question what is it like to have COPD and situated in Van Manen's phenomenology of practice. Experiential material was gathered through phenomenological interviews. Four themes emerged from the lived experiences of patients living with COPD: breath as a possibility; being vigilant; fighting a losing battle; and feeling isolated from others. For patients with COPD, breathing becomes ever-present and shifts from the invisible background of daily living to the central activity around which everyday life is organised. COPD patients always monitor their own breath and scrutinise the environment on possible dangers that can affect their breathing. Whenever moving or being involved in an activity, a part of their mind is preoccupied with the breathing. Although COPD patients realise that no amount of good behaviour will matter and that the decline of their lungs is inevitable, they make every effort to take good care of their body. They anticipate and avoid triggers of breathlessness isolating them from social interactions and activities. The appearance of the body as a source of social embarrassment also has an isolating effect. This study shows that breathlessness is a constant horizon that frames the experience of COPD patients. It is a limiting factor and determines their entire life. A more profound understanding of these experiences in healthcare professionals will contribute to person-centred care for COPD patients.

Introduction We present a case series of six treatment‐naive patients with clinical phenotypes compatible with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy without electrodiagnostic features of demyelination but with abnormal peripheral ultrasound findings who responded to treatment. Methods All six patients underwent a complete set of ancillary investigations, including extensive nerve conduction studies. We also performed standardized nerve ultrasound of median nerves and brachial plexus as part of a larger effort to evaluate diagnostic value of sonography. Results Nerve conduction studies did not show conduction block or other signs of demyelination in any of the six patients. Sonographic nerve enlargement was present in all patients and was most prominent in proximal segments of the median nerve and brachial plexus. Treatment with intravenous immunoglobulin resulted in objective clinical improvement. Discussion Our study provides evidence that nerve ultrasound represents a useful complementary diagnostic tool for the identification of treatment‐responsive inflammatory neuropathies.

BackgroundMultiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was to explore the contribution of personality traits in explaining occupational functioning in MS.Methods241 participants with relapsing-remitting MS (78% female, median age: 42.0 years, median EDSS: 2.0) and 60 healthy controls (70% female, median age: 45.0 years) underwent neuropsychological and neurological examinations and completed questionnaires. Multivariate logistic and linear regression analyses were conducted to examine relations between personality traits and self-reported occupational functioning, while accounting for known correlates.ResultsPersonality traits were not associated with self-reported occupational functioning when correcting for known correlates. A higher impact of fatigue (B = -0.05, p = .005 and B = -0.04, p = .009) and depression (B = -0.22, p = .008 and B = -0.21, p = .01) were associated with no paid job (R2 = 0.13) and considering to reduce work hours (R2 = 0.12). A higher impact of fatigue (B = -0.05, p = .008, β = 0.46, p = .001 and β = −0.36, p = .001) was associated with absenteeism from work (R2 = 0.15), more presenteeism (R2 = 0.35) and lower work ability (R2 = 0.25). A higher impact of fatigue (β = 0.46, p = .001) and anxiety (β = 0.25, p = .001) were associated with more work difficulties (R2 = 0.54).ConclusionPersonality traits did not explain additional variance in self-reported occupational functioning in persons with relapsing-remitting MS with mild disability. The impact of fatigue was the main and most consistent correlate of occupational functioning, often combined with depression or anxiety. Total explained variance of the models was limited, emphasizing the need to additionally examine other (contextual) factors when considering occupational challenges in MS.

Background and objective Nerve ultrasound is a promising new tool in chronic inflammatory neuropathies. The aim of this study was to determine its prognostic value in a prospective multicenter cohort study including incident and prevalent patients with CIDP and MMN. Methods We enrolled 126 patients with CIDP, and 72 with MMN; 71 were treatment-naive. Patients with chronic idiopathic axonal polyneuropathy (CIAP; n = 35) were considered as disease controls. Standardized neurological examination, questionnaires, and nerve ultrasonography were obtained at time of inclusion and 1-year follow-up. Nerve size development over time and correlation between nerve size and clinical outcome measures were determined using linear mixed effects models. Results Nerve size development over time was heterogeneous. Only in MMN was there a correlation between C5 nerve root size and deterioration of grip strength (-1.3 kPa/mm2 (95% confidence interval [CI] -2.3 to -0.2). No other significant correlations between nerve size and clinical outcome measures were found. In MMN, presence of nerve enlargement at inclusion predicted deterioration of grip strength, and MMN patients with enlargement confined to the brachial plexus seemed to have more favorable outcomes. No other predictive effects of sonographic nerve size were found. Conclusions The present study indicates that the natural course of nerve size development in CIDP and MMN is heterogeneous, and that the prognostic value of sonographic nerve enlargement is limited. It had some predictive effect in patients with MMN. Further research in specific subgroups of chronic inflammatory neuropathy is necessary to determine the usefulness of nerve ultrasonography after the diagnostic phase.

OBJECTIVES Median nerve enlargement in leprosy seems to be more proximal than in carpal tunnel syndrome (CTS), but this feature has not been studied systematically. The aim of the study was to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS. MATERIALS AND METHODS Transverse sections of the median nerve were recorded from wrist to the mid-forearm (at distal wrist crease and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) in patients with leprosy, CTS and healthy subjects using high-resolution ultrasound. RESULTS Twenty-six patients each with leprosy and CTS were compared with healthy controls. Patients with leprosy included 6 (23.1%), 7 (26.9%), 7 (26.9%) and 6 (23.1%) patients with borderline tuberculoid, borderline-borderline, borderline lepromatous and lepromatous leprosy, respectively. Cross-sectional area (CSA) of median nerve was increased in all patients with leprosy as compared to healthy controls at all points of measurement. CSA was higher among patients with leprosy as compared to CTS at all points except at the wrist. In patients with leprosy, the maximal enlargement was noted 2-cm (M1) proximal to the wrist crease with gradual tapering of the CSA proximally (p

Contains fulltext : 238533.pdf (Publisher’s version ) (Open Access) The addition of ultrasound (US) to electrodiagnostic (EDX) tests can significantly enhance the accuracy of testing for ulnar neuropathy at the elbow (UNE). We aimed to obtain expert consensus to guide clinicians on the combined use of EDX and US in UNE investigation. Consensus was achieved using the Delphi method. Two consecutive anonymised questionnaires were submitted to 15 experts, who were asked to choose their level of agreement with each statement. Consensus was pre-defined as ≥ 80% rating agreement. The experts concluded that all investigations of UNE should include both nerve conduction studies and US. There was consensus that US should include cross-sectional area measurement and assessment of nerve mobility at the elbow, and that the entire ulnar nerve should be imaged. This study defined expert opinion on the 'core' techniques that should be used routinely in the UNE investigation using EDX and US. Areas with lack of consensus highlighted some controversial issues in the current use of these diagnostic modalities and the need for future research. This document is an initial step to guide clinicians on the combined investigation of UNE using EDX and US, to be regularly updated as new research emerges.

Background Cognitive functioning has been linked to employment outcomes in multiple sclerosis (MS) in cross-sectional studies. Longitudinal studies are however lacking and previous studies did not extensively examine executive functioning. Objectives We examined whether baseline cognitive functioning predicts a change in employment status after 2 years, while taking into account mood, fatigue and disability level. Methods A total of 124 patients with relapsing-remitting MS (pwMS) and 60 healthy controls were included. They underwent neurological and neuropsychological examinations and completed online questionnaires. PwMS were divided into a stable and deteriorated employment status group (SES and DES), based on employment status 2 years after baseline. We first examined baseline differences between the SES and DES groups in cognitive functioning, mood, fatigue and disability level. A logistic regression analysis was performed, with change in employment status (SES/DES) as dependent variable. Results The DES group included 22% pwMS. Group differences were found in complex attention, executive functioning, self-reported cognitive functioning, fatigue and physical disability. More physical disability (OR = 1.90, p = 0.01) and lower executive functioning (OR = 0.30, p = 0.03) were retained as independent predictors of DES (R2 = 0.22, p ≤ 0.001). Conclusions Baseline physical disability and executive functioning, but none of the other variables, moderately predicted a deterioration in employment status 2 years later. Trial registration This observational study is registered under NL43098.008.12: ‘Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose’. This study is registered at the Dutch CCMO register (https://www.toetsingonline.nl). Electronic supplementary material The online version of this article (10.1007/s10072-019-03999-w) contains supplementary material, which is available to authorized users.

For people living with multiple sclerosis (MS), one’s own body may no longer be taken for granted but may become instead an insistent presence. In this article, we describe how the body experience of people with MS can reflect an ongoing oscillation between four experiential dimensions: bodily uncertainty, having a precious body, being a different body, and the mindful body. People with MS can become engaged in a mode of permanent bodily alertness and may demonstrate adaptive responses to their ill body. In contrast to many studies on health and illness, our study shows that the presence of the body may not necessarily result in alienation or discomfort. By focusing the attention on the body, a sense of well-being can be cultivated and the negative effects of MS only temporarily dominate experience. Rather than aiming at bodily dis-appearance, health care professionals should therefore consider ways to support bodily eu-appearance.

Ultrasound can be used to visualize pathology in the peripheral nerves of patients with polyneuropathy. Nerve enlargement is the most frequent pathology, but other abnormalities, including abnormal nerve echogenicity and vascularity, are also encountered. This monograph presents an overview of the role of nerve ultrasound in the evaluation and management of both inherited and acquired polyneuropathies. A description of the sonographic techniques and common abnormalities is provided, followed by a presentation of typical findings in different neuropathies. Scoring systems for characterizing the presence and pattern of nerve abnormalities as they relate to different polyneuropathies are presented. Muscle Nerve 57: 716-728, 2018.

Alemtuzumab is a lymphocyte-depleting antibody and one of the most effective treatments for relapsing multiple sclerosis. However, it also causes loss of immune-tolerance leading to secondary autoimmunity and marked anti-drug antibody responses. Although these anti-drug responses have been reported to be of no significance, we hypothesized that they will affect the depleting capacity and treatment response in some individuals. This was found following analysis of the regulatory submission of the pivotal phase III trials, which was obtained from the European Medicines Agency. At the population level there was lack of influence of 'ever-positive' alemtuzumab-specific antibody responses on lymphocyte depletion, clinical efficacy and adverse effects during the 2-year trial. This was not surprising as no one before the first infusion, and only 0·6% of people before the second-infusion, had pre-infusion, neutralizing antibodies (NAbs). However, at the individual level, NAbs led to poor lymphocyte depletion. Importantly, it was evident that 31% of people had NAbs and 75% had binding antibodies at the end of treatment-cycle 2, which suggests that problems may occur in people requiring additional alemtuzumab cycles. In addition, we also identified individuals, following 'post-marketing' alemtuzumab use, whose lymphocyte level was never effectively depleted after the first infusion cycle. Hence, although alemtuzumab depletes lymphocytes in most individuals, some people fail to deplete/deplete poorly, probably due to biological-response variation and NAbs, and this may lead to treatment failure. Monitoring depletion following infusion and assessment of the neutralizing response before re-infusion may help inform the decision to retreat or switch therapy to limit treatment failure.

Introduction Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. Methods We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). Results A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. Discussion HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018.

Introduction: We quantified intraneural blood flow (INBF) in 18 patients with end-stage kidney disease (ESKD) and examined its relationship with nerve size, neuropathy severity and nerve excitability parameters. Methods: Sonographic measurements of the median nerve were performed at the same site before and after haemodialysis. INBF was quantified by analysing power Doppler sonograms to obtain the vessel score (VSc) and maximum perfusion intensity(MPI). Corresponding median motor nerve excitability studies were performed. Neuropathy severity was assessed using total neuropathy score (TNS). Results: 39% of ESKD patients had detectable INBF compared to none in the control group (P

BACKGROUND: Cognitive deficits affect up to 70% of all patients with Multiple Sclerosis (MS) and have a significant impact on quality of life. Cognitive assessments need to be performed by a neuropsychologist and are often time-consuming, hampering timely identification and adequate monitoring of cognitive decline in MS.OBJECTIVE: To develop a time-efficient, unsupervised, digital tool to screen for cognitive deficits in MS.METHODS: A digital (adjusted) version of the Brief International Cognitive Assessment for MS, including the Symbol Digit Modalities Test (SDMT, information processing speed), the California Verbal Learning Test (CVLT-II, verbal memory) and the Spatial Recall Test (SPART, visuospatial memory) was developed: Multiple Screener (intellectual property of Sanofi Genzyme). Firstly, the clarity and feasibility of the tool was confirmed by 16 patients with MS (mean age 50.9 years (SD 9.4, range 37-68). Next, in 60 healthy controls (HCs, mean age 44.5 years (SD 14.0, range 18-67), intraclass correlation coefficients (ICC) were calculated to describe how strongly the digital version resembled the paper and pencil-based assessment. Finally, 236 HCs (mean age 42.8 years (SD 12.8, range 18-69) were included to obtain norm scores for each test.RESULTS: ICCs between digital and paper and pencil-based assessment were excellent to good (SDMT (ICC 0.79, confidence interval (CI) 0.67-0.87); CVLT-II (ICC 0.77, CI 0.64-0.85); SPART (ICC 0.61, CI 0.42-0.75)). For each test, a regression-based correction for the effect of age was applied on the raw scores before converting them to norm Z-scores. Additionally, the SDMT scores needed correction for education and the CVLT-II for education and sex (subgroups were created).CONCLUSIONS: Performance on an adjusted, digital version of the BICAMS correlates highly with the standard paper-and-pencil based test scores in HCs. Multiple Screener is an unsupervised, digital tool, with available norm scores, ultimately allowing for easy monitoring of cognitive decline in patients with MS.

BackgroundRecent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and occupational functioning. Our objectives are: (1) to examine whether empathy differs between individuals with MS and healthy controls, (2) to examine relations between empathy and cognitive, psychological and occupational functioning.Methods278 individuals with MS (relapsing-remitting subtype) and 128 healthy controls from the MS@Work study participated in this investigation. The participants completed questionnaires about demographics, cognitive, psychological and occupational functioning, and underwent neurological and neuropsychological examinations. Mann-Whitney U-tests were used to examine group differences in empathy. Pearson and Spearman rank correlation analyses were used to examine relations between empathy and the other measures.ResultsEmpathy did not differ between individuals with MS and healthy controls. In individuals with MS, higher empathy was correlated with a higher educational level (X2(df) = 13.2(2), p = 0.001), better verbal learning (r = 0.20, p = 0.001), less symptoms of depression (r=−0.21, p = 0.001), higher extraversion (r = 0.25, p ≤ 0.001), agreeableness (r = 0.55, p ≤ 0.001) and conscientiousness (r = 0.27, p ≤ 0.001) and better occupational functioning in terms of work scheduling and output demands (r = 0.23, p = 0.002) and less cognitive/psychological work barriers (r = −0.21, p = 0.001). In healthy controls, higher empathy was correlated with less symptoms of depression (r = −0.34, p ≤ 0.001), less fatigue (r = −0.37, p ≤ 0.001), higher agreeableness (r = 0.59, p ≤ 0.001) and better occupational functioning in terms of work ability as compared to lifetime best (r = 0.28, p = 0.001) and less cognitive/psychological work barriers (r = −0.34, p ≤ 0.001). Empathy did not differ between unemployed and employed individuals with MS or healthy controls.ConclusionEmpathy did not differ between individuals with MS and healthy controls. Within both investigated groups, higher empathy was weakly to moderately correlated with less symptoms of depression, higher agreeableness and better occupational functioning. We also found unique correlations for empathy within the investigated groups. Longitudinal studies are needed to further examine social cognition in relation to cognitive, psychological and occupational functioning in both individuals with MS and healthy controls. It would be particularly interesting to concurrently examine changes in the brain network involved with social cognition.

ObjectiveTo validate the diagnostic accuracy of a previously described short sonographic protocol to identify chronic inflammatory neuropathy (CIN), including chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis Sumner syndrome, and multifocal motor neuropathy (MMN), and to determine the added value of nerve ultrasound to detect treatment-responsive patients compared to nerve conduction studies (NCS) in a prospective multicenter study.MethodsWe included 100 consecutive patients clinically suspected of CIN in 3 centers. The study protocol consisted of neurologic examination, laboratory tests, NCS, and nerve ultrasound. We validated a short sonographic protocol (median nerve at forearm, upper arm, and C5 nerve root) and determined its diagnostic accuracy using the European Federation of Neurological Societies/Peripheral Nerve Society criteria of CIDP/MMN (reference standard). In addition, to determine the added value of nerve ultrasound in detecting treatment-responsive patients, we used previously published diagnostic criteria based on clinical, NCS, and sonographic findings and treatment response (alternative reference standard).ResultsSensitivity and specificity of the sonographic protocol for CIN according to the reference standard were 87.4% and 67.3%, respectively. Sensitivity and specificity of this protocol according to the alternative reference standard were 84.6% and 72.8%, respectively, and of NCS 76.1% and 93.4%. With addition of nerve ultrasound, 44 diagnoses of CIN were established compared to 33 diagnoses with NCS alone.ConclusionsA short sonographic protocol shows high diagnostic accuracy for detecting CIN. Nerve ultrasound is able to detect up to 25% more patients who respond to treatment.Classification of evidenceThis multicenter study provides Class IV evidence that nerve ultrasound improves diagnosis of CIN.

Purpose: The current study aimed to evaluate the psychometric properties of the Dutch version of the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23). Methods: Two hundred and thirty-nine employed persons with multiple sclerosis (MS) and 59 healthy controls completed the MSWDQ-23. To verify the factor structure, a confirmatory factor analysis was conducted. To assess construct validity, the MSWDQ-23 scores were correlated to measures of physical disability, fatigue, cognitive and neuropsychiatric problems, depression, health-related quality of life, and work-related variables. MSWDQ-23 scores were compared within different age groups, gender, education levels, and job types. Predictive validity was assessed using a logistic regression analysis to predict a deterioration in employment status after one year based on MSWDQ-23 scores. Results: The internal consistency of the MSWDQ-23 was acceptable (α = 0.913, 95% CI = 0.897–0.928) and the results indicated a fair fit. The MSWDQ-23 showed acceptable construct validity, confirming 94% of the hypotheses. The total scale and the psychological/cognitive subscale were able to predict a deterioration in employment status after one year (χ2(1)=18.164, p Conclusions: The Dutch version of the MSWDQ-23 is a valid and internally consistent instrument to measure self-reported work difficulties in persons with MS.Implications for rehabilitationThe Dutch version of the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) is a reliable and valid tool to measure self-reported work difficulties in people with multiple sclerosis (MS).More psychological and cognitive work difficulties are predictive of a deteriorated employment status after one year.The MSWDQ-23 is a helpful tool for researchers and (occupational) health professionals to identify current work difficulties in persons with MS and identify persons at risk for a deterioration in employment one year later. The Dutch version of the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) is a reliable and valid tool to measure self-reported work difficulties in people with multiple sclerosis (MS). More psychological and cognitive work difficulties are predictive of a deteriorated employment status after one year. The MSWDQ-23 is a helpful tool for researchers and (occupational) health professionals to identify current work difficulties in persons with MS and identify persons at risk for a deterioration in employment one year later.

In patients with chronic disorders, control self-efficacy is the confidence with managing symptoms and coping with the demands of illness. Can do treatment (CDT) is an intensive, 3-day, social cognitive theory-based, multidisciplinary treatment that focuses on identification of stressors, goal setting, exploration of boundaries, and establishment of new boundaries. An uncontrolled study showed that patients with relapsing remitting multiple sclerosis (RRMS) and low-disability had improved control self-efficacy six months after CDT. Hence, in a 6-month, single-centre, randomized (1:1), unmasked, controlled trial in RRMS patients with Expanded Disability Status Scale (EDSS) score ≤4.0, we compared CDT with no intervention and the option to receive CDT after completion of study participation. Follow-up assessments were at one, three and six months. Primary endpoint was control self-efficacy (Multiple Sclerosis Self-Efficacy Scale Control [MSSES-C] (minimum 90, maximum 900) at six months. Secondary endpoints were functional self-efficacy (MSSES-F), participation and autonomy (Impact on Participation and Autonomy questionnaire [IPA]), health-related quality of life (MS Quality of Life-54 Items questionnaire [MSQoL-54]), anxiety, depression (Hospital Anxiety and Depression Scale [HADS]) and coping skills (Utrecht Coping List [UCL]) at six months. Tertiary endpoint was care-related strain on support partners (Caregiver Strain Index) at six months. Of the 158 patients that were included, 79 were assigned to CDT and 79 to the control group. Two CDT patients discontinued treatment prematurely. Sixty-one (77%) control patients chose to receive CDT after study participation. Intention-to-treat ANCOVA analyses were performed with follow-up values as dependent, and condition, baseline values, disease duration and gender as independent variables. The mean (standard deviation [SD]) MSSES-C score in the CDT group vs. control group at baseline was 468 (162) vs. 477 (136), and at six months 578 (166) vs. 540 (135) (p = 0.100). Secondary and tertiary endpoints did not differ between groups, except for the UCL palliative reaction score being slightly higher in the CDT group (p = 0.039). On post hoc analyses the MSSES-C score at one and three months was higher in the CDT vs. control group: 597 (114) vs. 491 (131) (p

ObjectiveTo examine the diagnostic accuracy of nerve ultrasound in a prospective cohort of consecutive patients with a clinical suspicion of chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy, Lewis-Sumner syndrome, and multifocal motor neuropathy, and to determine the added value in the detection of treatment-responsive patients.MethodsBetween February 2015 and July 2018, we included 100 consecutive incident patients with a clinical suspicion of chronic inflammatory neuropathy. All patients underwent nerve ultrasound, extensive standardized nerve conduction studies (NCS), and other relevant diagnostic investigations. We evaluated treatment response using predefined criteria. A diagnosis of chronic inflammatory neuropathy was established when NCS were abnormal (fulfilling criteria of demyelination of the European Federation of Neurological Societies/Peripheral Nerve Society) or when the degree of nerve enlargement detected by sonography was compatible with chronic inflammatory neuropathy and there was response to treatment.ResultsA diagnosis of chronic inflammatory neuropathy was established in 38 patients. Sensitivity and specificity of nerve ultrasound and NCS were 97.4% and 69.4% and 78.9% and 93.5%, respectively. The added value of nerve ultrasound in detection of treatment-responsive chronic inflammatory neuropathy was 21.1% compared to NCS alone.ConclusionsNerve ultrasound and NCS are complementary techniques with superior sensitivity in the former and specificity in the latter. Addition of nerve ultrasound significantly improves the detection of chronic inflammatory neuropathies. Therefore, it deserves a prominent place in the diagnostic workup of chronic inflammatory neuropathies.Classification of evidenceThis study provides Class IV evidence that nerve ultrasound is an accurate diagnostic tool to detect chronic inflammatory neuropathies.

AIMS To undertake sonographic assessment of nerve blood flow in people with Type 2 diabetes and correlate the findings with neuropathy severity scores and electrophysiological measurements. METHODS Median and tibial nerve ultrasound scans were undertaken in 75 people with diabetes and 30 aged-matched controls without diabetes, using a high-resolution linear probe at non-entrapment sites. Nerve blood flow was quantified using power Doppler techniques to obtain the vessel score and the maximum perfusion intensity. Neuropathy severity was assessed using a total neuropathy score. RESULTS Diabetic nerves had higher rates of nerve blood flow detection (28%) compared to the control group (P < 0.0001). Significant correlations were found between nerve blood flow measurements and nerve size (P

BackgroundMultiple sclerosis (MS) is a chronic disorder of the central nervous system with an unpredictable disease course. Life partners often become caregivers, which can be both rewarding and challenging, as the caregiver's physical and mental health is often negatively affected. Previous studies on caregiver strain focused on caregivers of persons with MS with relatively high disability levels, while caregiver strain may already be experienced by life partners living with mildly disabled persons with MS.ObjectiveThe current study examines factors associated with caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS.MethodsWe included 173 persons with relapsing-remitting MS (79% female; mean age 42.8 years; 90% employed; median EDSS 2.0) and their life partners. The life partners completed questionnaires on caregiver strain and neuropsychiatric and cognitive functioning of the person with MS. The persons with MS completed questionnaires about demographics, fatigue, personality, physical, cognitive and neuropsychiatric functioning, and underwent neuropsychological and neurological examinations. A linear regression analysis was conducted to examine predictors of caregiver strain.Results24% of the life partners experienced above average levels of caregiver strain. A multivariate linear regression analysis revealed that a higher age of the person with MS (β = 0.16, p = 0.04), more physical disability (β = 0.17 p = 0.04), more cognitive and neuropsychiatric problems of the person with MS as reported by the life partner (β = 0.33, p = 0.001) and higher severity of neuropsychiatric symptoms as reported by the life partner (β = 0.32, p = 0.001) were associated with higher caregiver strain (R2 = 0.49).ConclusionHigher caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS was primarily associated with cognitive and neuropsychiatric problems of the person with MS.

INTRODUCTION The best treatment strategy for mild ulnar neuropathy at the elbow (UNE) is not known, due to lack of trials comparing surgery vs conservative treatment. METHODS We recruited patients with clinical symptoms and signs of mild UNE and an electrophysiologically or sonographically confirmed diagnosis. Patients were randomly allocated to either in situ decompression or conservative treatment. The primary outcome was the proportion of patients with subjective symptom improvement at short-term (3 months) and long-term (6-12 months) follow-up. RESULTS One hundred seventeen patients were included: 56 and 61 patients were allocated to surgery and conservative treatment, respectively. A larger proportion of surgically treated patients showed improvement at short-term follow-up (85% vs 50%; odds ratio, 5.6; P < .001), but no differences were observed at long-term follow-up. DISCUSSION In situ decompression for mild UNE may result in faster relief of symptoms when compared with conservative treatment, but at long-term follow-up no differences were observed.

Aims: This trial-based economic evaluation (EE) assesses from a societal perspective the cost-effectiveness of an intensive 3-day cognitive theory-based intervention (CDT), compared to care-as-usual, in patients with relapsing remitting multiple sclerosis (RRMS) and low disability (Expanded Disability Status Scale [EDDS] score

Introduction. Median nerve enlargement in leprosy using high-resolution ultrasound seems to be more proximal than in carpal tunnel syndrome (CTS), which might be an important discriminating sign, but has not been studied systematically. The aim of this study is to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS. Methods. Transverse sections of the median nerve were recorded from wrist until the forearm (at distal wrist crease, and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) and at mid arm and forearm in patients with leprosy, CTS and healthy subjects. Results. Twenty-six patients each with leprosy and CTS were compared with healthy controls. Patients with leprosy included 6 (23%), 7 (26.9%), 7 (26.9%) and 6 (23.1%) patients with borderline-tuberculoid, borderline-borderline, borderline-lepromatous and lepromatous leprosy respectively. Cross-sectional area (CSA) of median nerve was increased in all patients with leprosy as compared to healthy controls at all points of measurement. CSA was higher among patients with leprosy as compared to CTS at all points except at the wrist. In patients with leprosy, the maximal enlargement was noted 2-cm (M1) proximal to the wrist crease with gradual tapering of the CSA proximally (p Conclusion. Enlargement of median nerve 2-cm proximal to the distal wrist crease is a characteristic feature that distinguishes leprosy from CTS. This important finding can be used at point-of-care ultrasound to identify patients with leprosy.

Introduction We aimed to identify prognostic factors in ulnar neuropathy at the elbow (UNE) and developed a scoring system to predict the prognosis. Methods We collected baseline clinical, electrophysiological, and ultrasonographical data from 2 cohorts. The outcome for all patients were determined on follow up. Prognostic factors were determined using single and multiple variable analyses. A points system was developed to determine the risk for an unfavorable outcome. Results Of 220 patients with UNE 178 (81%) could be re-evaluated. Four variables were retained in the prediction model for a points system. An unfavorable outcome was associated with right sided UNE, more severe weakness of the abductor digiti minimi (ADM), and more pronounced ulnar nerve thickening. Compound muscle action potential amplitude reduction across the elbow ≥ 16% (particularly ≥ 50%) was associated with a more favorable outcome. Discussion Outcome in UNE may be predicted by scoring 4 parameters. This article is protected by copyright. All rights reserved.

Early diagnosis and treatment of leprosy and leprosy reactions are essential to prevent stigmatizing deformities and disability. Although the incidence of leprosy has decreased enormously, grade 2 disability due to nerve injury has remained the same. New tools are needed to better diagnose and monitor leprosy reactions and associated neuritis and this study assessed whether high-resolution sonography (HRUS) can be used as such a tool.During a prospective follow-up period of 2 years at regular intervals, we performed clinical examination to assess sensory and motor function and HRUS of the four main peripheral nerves in 57 patients, of whom 36 were with reactions and 21 were without reactions. Normative data of the cross-sectional area (CSA) of these nerves were obtained from 55 healthy subjects (HS). Color Doppler (CD) was used to study blood flow in the nerves.At the baseline visit and during follow-up, all four nerves were significantly thicker in patients with leprosy reactions in comparison to HS (p 0.0001) and to a lesser extent also in comparison to patients without reactions ranging from a p-value of 0.05 to 0.0001 in the different nerves tested. During follow-up, the nerve size did not change significantly in patients without reactions, while it decreased significantly in patients with reactions. At baseline, endoneural blood flow was present only in patients with reactions. This occurred in 20 of the 36 (55 %) patients (49 nerves) and decreased to only 1 patient (2.7 %) at the end of the follow-up period.This prospective study demonstrates the ability of HRUS to monitor disease activity and the effect of treatment in patients with leprosy reactions by determining changes in nerve size and vascularity, which are indicators of peripheral nerve involvement and damage.ZIEL: Frühe Diagnose und Therapie der Lepra und der Lepra-Reaktionen ist entscheidend, um stigmatisierende Entstellungen und Behinderungen zu verhindern. Obwohl die Lepra-Inzidenz immens gesunken ist, ist eine Behinderung 2. Grades aufgrund der Nervenschädigung gleich häufig geblieben. Neue Verfahren für eine bessere Diagnose und Überwachung der Lepra-Reaktionen und der assoziierten Neuritis sind erforderlich, daher überprüft diese Studie, ob HRUS hierfür eingesetzt werden kann.Während eines prospektiven Nachuntersuchungszeitraums von 2 Jahren mit gleichmäßigen Intervallen führten wir bei 57 Patienten eine klinische Untersuchung der sensorischen und motorischen Funktionen und HRUS der vier peripheren Hauptnerven durch, von denen 36 Reaktionen und 21 keine Reaktionen zeigten. Die normativen Werte der Querschnittsregion (CSA) dieser Nerven wurden bei 55 Gesunden erhoben. Farbdopplersonografie wurde durchgeführt, um den Blutfluss in den Nerven zu ermitteln.Beim Erstbesuch und während der Folgeuntersuchungen waren bei allen Patienten mit Lepra-Reaktionen im Vergleich zu gesunden alle vier Nerven signifikant dicker (p 0,0001) und in geringerem Maße auch im Vergleich zu Patienten ohne Reaktionen, die in einem p-Wert-Bereich zwischen 0,05 und 0,0001 für die verschiedenen untersuchten Nerven lagen. Während der Folgeuntersuchungen veränderte sich bei Patienten ohne Reaktion die Größe der Nerven kaum, während sie bei Patienten mit Reaktionen signifikant kleiner wurden. Bei Erstaufnahme war der endoneurale Blutfluss nur bei Patienten mit Reaktionen vorhanden, dies traf für 20 (55 %) der 36 Patienten zu (49 Nerven) und sank auf nur einen Patienten (2,7 %) am Ende des Nachsorgezeitraums ab.Diese prospektive Studie zeigt die Möglichkeit des HRUS, die Erkrankungsaktivität und den Therapieerfolg bei Patienten mit Lepra-Reaktionen zu überwachen, indem die Veränderungen der Nervengröße und Durchblutung bestimmt werden, welche Hinweise auf eine Beteilung der peripheren Nerven und deren Schädigung geben.

Background Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. Objective Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. Methods This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. Results Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. Conclusions The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. International Registered Report Identifier (IRRID) DERR1-10.2196/16162

ObjectiveTo determine interobserver variability of nerve ultrasound in peripheral neuropathy in a prospective, systematic, multicenter study.MethodsWe enrolled 20 patients with an acquired chronic demyelinating or axonal polyneuropathy and 10 healthy controls in 3 different centers. All participants underwent an extensive nerve ultrasound protocol, including cross-sectional area measurements of median, ulnar, fibular, tibial, and sural nerves, and brachial plexus. Real-time image acquisition was performed blind by a local and a visiting investigator (reference). Five patients were investigated using different types of sonographic devices. Intraclass correlation coefficients were calculated, and a random-effects model was fitted to identify factors with significant effect on interobserver variability.ResultsSystematic differences between measurements made by different investigators were small (mean difference 0.11 mm2 [95% confidence interval 0.00–0.23 mm2]). Intraclass correlation coefficients were generally higher in arm nerves (0.48–0.96) than leg nerves (0.46–0.61). The hospital site and sonographic device did not contribute significantly to interobserver variability in the random-effects model.ConclusionsInterobserver variability of nerve ultrasound in peripheral neuropathy is generally limited, especially in arm nerves. Different devices and a multicenter setting have no effect on interobserver variability. Therefore, nerve ultrasound is a reproducible tool for diagnostics in routine clinical practice and (multicenter) research.

Purpose:In addition to becoming familiar with the life changing event of having a chronic illness and exploring its meaning in daily life, people with relapsing-remitting Multiple Sclerosis (RRMS) are faced with important decisions about immunomodulating treatment. Biomedical research on the use of Disease Modifying Therapies (DMTs) mostly focuses on adherence, conceptualized and understood as a behavioral act leading to a desired outcome. Less attention has been paid to the meaning for a person with RRMS of starting and continuing the use of DMTs. Studies on the experiences of people with RRMS taking orally administered DMTs are lacking. The aim of this phenomenological study was to examine the experiences of people with RRMS taking oral medication. Methods: The study was guided by Interpretative Phenomenological Analysis (IPA) and Phenomenology of Practice. 25 persons with RRMS participated in in-depth interviews. Results: In general, participants of this study find themselves in alternating phases that vary by degree of experienced unfamiliarity or familiarity with concern to one's illness, one's changing body, and one's new life. The meaning of taking medication is closely related to these phases. Conclusions: Adherence serves a purpose in the lifeworlds of participants. Medication is the embodiment of this purpose. The pill has inherent meaning.

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes.METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'.RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34).CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes.TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014.

Leprosy is the most common treatable peripheral nerve disorder worldwide, with periods of acute neuritis leading to functional impairment of limbs and stigmatizing deformities. The nerve involvement in leprosy reactions, if recognized early and promptly treated with steroids and nerve release surgery, can be reversible. Currently, the nerve assessment in leprosy relies mainly on clinical assessment and nerve conduction studies. High-resolution ultrasonography (HRUS) of peripheral nerves is finding wider application in the differential diagnosis of peripheral neuropathy. HRUS provides a noninvasive tool that gives information on location and degree of nerve enlargement, nerve morphologic alterations, echo texture, fascicular pattern, and vascularity of the nerve, which mirrors the histologic changes. HRUS is amenable to studying structural changes in nerve sites that cannot be biopsied for histopathologic examination and is more cost effective than magnetic resonance imaging. So far other there are only five studies available on the sonographic findings in leprosy. These findings are reviewed and the technique of HRUS is described in this paper, with a recommendation of a standard protocol and proforma.

Quantitative assessment of nerve echogenicity using the MaxEntropy, RenyiEntropy and Yen methods has shown promise in the assessment of ulnar neuropathy at the elbow. The purpose of this study was to determine the clinical usefulness of quantitative echogenicity measurement when using these three automatic thresholding methods in the evaluation of patients with common fibular (CF) neuropathy.High-resolution ultrasonography (HRUS) images of the CF nerve from 45 patients with CF neuropathy were compared to 42 healthy controls.With all three methods patients with CF neuropathy had significantly higher mean hypoechoic fraction than healthy controls at the level of the fibular head (FH): MaxEntropy 87.4% versus 71.9% (p0.001), RenyiEntropy 84.7% versus 68% (p0.001) and Yen 87.6% versus 68.2% (p0.001). Patients with CF neuropathy could be differentiated from healthy controls at a hypoechoic fraction cut-off point of 82% (MaxEntropy), 80% (RenyiEntropy) and 80% (Yen) with a sensitivity of 82%, 82% and 84% respectively, and a specificity of 93%, 95% and 83% respectively. Similar results were found for sonographic measurements above the FH.Quantitative assessment of nerve echogenicity using the MaxEntropy, RenyiEntropy and Yen methods can be used to distinguish between patients with CF neuropathy and healthy controls with high sensitivity and specificity.These three proven automatic thresholding methods can be used to assess nerve echogenicity in future studies. Quantitative echogenicity assessment with HRUS shows promise for the future as a potential diagnostic tool in daily clinical practice.