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ObjectiveTo study survival and to characterize long-term functional impairments and health-related quality of life (HRQOL) of patients with Lambert-Eaton myasthenic syndrome (LEMS).MethodsIn this observational study, survival of patients with LEMS, separately for nontumor (NT) and small cell lung cancer (SCLC), was compared to that of the Dutch general population and patients with SCLC. Disease course in patients with LEMS was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed.ResultsWe included 150 patients with LEMS. Survival was similar to that of the general population in 65 patients with NT-LEMS. Tumor survival was significantly longer in 81 patients with SCLC-LEMS compared to patients with non-LEMS SCLC (overall median survival 17 vs 7.0 months, p < 0.0001). At diagnosis, 39 (62%) of 63 patients with complete follow-up data were independent for activities of daily living, improving to 85% at the 1-year follow-up. The physical HRQOL composite score (55.9) was significantly lower than in the general population (76.3, p < 0.0001) and comparable to that of patients with myasthenia gravis (60.5). The mental HRQOL composite score was 71.8 in patients with LEMS, comparable to that of the general population (77.9, p = 0.19) and patients with myasthenia gravis (70.3).ConclusionsThis study shows that patients with NT-LEMS have normal survival. Patients with SCLC-LEMS have an improved tumor survival, even after correction for tumor stage. A majority of patients with LEMS report a stable disease course and remain or become independent for self-care after treatment.

In this retrospective study, we conducted a clinico-genetic analysis of patients with autosomal recessive limb-girdle muscular dystrophy (LGMD) and Miyoshi muscular dystrophy (MMD). Patients were identified at the tertiary referral centre for DNA diagnosis in the Netherlands and included if they carried two mutations in CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TRIM32, FKRP or ANO5 gene. DNA was screened by direct sequencing and multiplex ligand-dependent probe amplification (MLPA) analysis. A total of 244 patients was identified; 68 LGMDR1/LGMD2A patients with CAPN3 mutations (28%), 67 sarcoglycanopathy patients (LGMDR3-5/LGMD2C-E) (27%), 64 LGMDR12/LGMD2L and MMD3 patients with ANO5 mutations (26%), 25 LGMDR2/LGMD2B and MMD1 with DYSF mutations (10%), 21 LGMDR9/LGMD2I with FKRP mutations (9%) and one LGMDR8/LGMD2H patient with TRIM32 mutations (

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.

Measuring vibration perception threshold (VPT) accurately classifies and quantifies the severity of loss of vibration perception. A biothesiometer (Bio-thesiometer (R); Bio Medical Instrument Co, Ohio, USA) appears to be the most suitable tool to determine VPT due to its low inter-rater variability and low occurence of adaption to the sensation. Different VPT values for a biothesiometer have been described, however, specification on age, height and different measurement locations is currently lacking. The objective of our study was to identify determinants of vibration perception in non-diabetic subjects, in order to provide individualized normal values of VPTs for clinical practice. Measurements of the vibration perception were performed on the big toes, insteps, lateral malleoli, and wrists. A total of 205 healthy subjects were included (108 (52.7%) males) with a median [interquartile range] age of 59 [51;64] (range 21-80) years. Mean height was 174.45 +/- 9.20 cm and mean weight was 82.94 +/- 14.84 kg, resulting in a mean BMI of 27.19 +/- 4.00 kg/m(2). In stepwise forward linear regression analyses, age (st. beta = 0.51, p

OBJECTIVE: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP.METHODS: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP- (HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels.RESULTS: sNfL levels were increased both in 10 AL/PNP+ patients (p I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p = .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age.CONCLUSION: sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis.

The globalization of healthcare has had a significant impact on healthcare delivery and human workforce development in many countries. Consequently, many educational institutions have had to revise the content of their medical curricula to focus on training and preparing future doctors to effectively cater to the needs of the “modern patient”. The focus covers broader aspects of medicine that include environmental and professional culture and the impact of socioeconomic inequalities on the delivery of healthcare. Therefore, in most global health (GH) education programs described, students undertake a specific part of their clinical rotation in a foreign (non-western) educational setting to facilitate authentic learning experiences within a resource-constrained environment. In this paper we present a unique Global Health program for medical interns between the University Medical Center Groningen, Netherlands and the Sint Elisabeth Hospital, Curaçao, Dutch Caribbean that has, for more than 50 years, been providing a one-year internship program as part of the formal Groningen curriculum. The program we describe, illustrates the essential requirements for best practice in GH education that fully complies with recently proposed GH program objectives and competencies. The characteristics of our long running program show the basic requirements necessary for sustainable and successful health education collaboration between institutions in high- and low/middle income countries. Finally, this program, which is part of a Dutch medical curriculum, not only provided unique global health learning experiences for the interns, but importantly also contributed to improving the general healthcare delivery services on the island of Curaçao as well.

Background Cultural differences might challenge the acceptance of the implementation of assessment formats that are developed in other countries. Acceptance of assessment formats is essential for its effectiveness; therefore, we explored the views of students and specialists on the practicality and impact on learning of these formats. This study was conducted to explore Indonesian students’ and specialists’ appreciation of the implementation of the Mini-Clinical Evaluation Exercise (Mini-CEX) in Indonesian clerkships. Methods This study was conducted at the Universitas Gadjah Mada, Indonesia. Participants were 52 students and 21 specialists in neurology and 78 students and 50 specialists in internal medicine. They were asked to complete a 19-item questionnaire that covered the characteristics of the mini-CEX such as its practicality, and the impact on learning and professional development. We used a Mann-Whitney U test to analyse the data. Results In total, 124 students (46 from neurology and 78 from internal medicine) and 38 specialists (13 from neurology and 25 from internal medicine) participated in this study. Students and specialists were positive about the practicality of the mini-CEX and the impact of this assessment format on learning and on professional development. The Mann-Whitney U test showed that there were no significant differences between students’ and specialists’ opinions on the mini-CEX, except for 2 items: specialists’ appreciation of direct observation (mean rank = 93.16) was statistically significantly higher than students’ appreciation of it (mean rank = 77.93; z = 2.065; p p Conclusion Students and specialists were positive about the mini-CEX in Indonesian clerkships, although it was developed and validated in another culture. We found only small differences between their appreciations, which could be explained by the patterns of specialist-student interaction in Indonesian culture as large power distance and low individualism country.

A patient with autoimmune myasthenia gravis and a clinical and serological follow-up of 13 years is described. In this unique case, serum samples were available up to two years before the clinical onset of the myasthenia gravis and showed gradual increase of acetylcholine receptor antibodies, starting two years before onset of the clinical symptoms.

Background: The aim of this study was to examine the stability and relative validity (RV) of the Neuromuscular Disease Impact Profile (NMDIP) using criterion-related groups. In a previous study the NMDIP-scales showed good internal consistency, convergent and discriminant validity. Known-groups analysis showed that the NMDIP discriminates between categories of extent of limitations.Methods: A cross-sectional postal survey study was performed on patients diagnosed with a NMD and registered at the Department of Neurology, University Medical Center Groningen, the Netherlands.Participants were asked to complete the preliminary NMDIP, the Medical Outcome study Short Form Questionnaire (SF-36), the World Health Organization Quality Of Life-abbreviation version (WHOQOL-bref), and two generic domain specific:measures the Groningen Activity Restriction Scale (GARS) and the Impact on Participation and Autonomy Questionnaire (IPAQ). The variables 'Extent of Limitations' and 'Quality of Life' were used to create criterion-related groups. Stability over time was tested using the Wilcoxon Signed Rank Test for paired samples and the intraclass-correlation coefficients for repeated measures. RV was examined by comparing the ability of NMDIP with generic multidimensional health impact measures, and domain specific measures in discriminating between criterion-related subgroups using the Kruskal-Wallis H-test.Results: Response rate was 70% (n = 702). The NMDIP-scales showed sufficient stability over time, and satisfactory or strong RV. In general, the NMDIP scales performed as well as or better than the concurrent measurement instruments.Conclusions: The NMDIP proved to be a valid and reliable disease-targeted measure with a broad scope on physical, psychological and social functioning.

Muscle-specific kinase (MuSK) myasthenia gravis (MG) is hallmarked by the predominant involvement of bulbar muscles and muscle atrophy. This might mimic amyotrophic lateral sclerosis (ALS) presenting with bulbar weakness. We encountered four cases of MuSK MG patients with an initial misdiagnosis of ALS. We analyzed the clinical data of the four misdiagnosed MuSK MG patients, and investigated the presence of MuSK autoantibodies in a group of 256 Dutch bulbar-onset ALS patients using a. recombinant MuSK ELISA and a standard MuSK radioimmunorecipitation assay. Clues for changing the diagnosis were slow progression, clinical improvement, development of diplopia and absence of signs of upper motor neuron involvement. No cases of MuSK MG were identified among a group of 256 bulbar ALS patients diagnosed according to the revised El Escorial criteria. A misdiagnosis of ALS in patients with MuSK MG is rare. We recommend to carefully consider the diagnosis of MuSK MG in patients presenting with bulbar weakness without clear signs of upper motor neuron dysfunction. (C) 2016 Elsevier B.V. All rights reserved.

Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness.We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA.Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies. (C) 2016 Elsevier B.V. All rights reserved.

This chapter describes signs and symptoms characteristic for postsynaptic neuromuscular junction diseases, how to validate them, and when to attribute them to myasthenia or another neurological disease. Non-motor symptoms in myasthenia will be discussed separately with a special reference to “fatigue.” We propose a bedside examination policy. The clinical course of myasthenia and how it may be influenced by external factors are described; several clinical subgroups are identified: congenital vs. acquired, anti-AChR vs. anti-MuSK vs. seronegative, pure ocular vs. generalized, thymoma vs. no thymoma, and early onset vs. late onset in a-AChR+ patient.

Purpose: People with neuromuscular disease experience lower quality of life levels than people from the general population. We examined the prevalence and severity of a broad range of neuromuscular disease-related disabilities and their impact on health-related quality of life. Materials and methods: A cross-sectional postal survey study was conducted among patients diagnosed with neuromuscular disease. Patients completed the Neuromuscular Disease Impact Profile, a disease-related disability impact questionnaire, and two generic health-related quality of life questionnaires: the medical outcome study Short Form Questionnaire and the World Health Organization Quality of Life-bref. The impact of disabilities on quality of life was estimated using multiple regression analyses. Results: Six hundred sixty two patients (68% response rate) completed the questionnaires. There were no differences in quality of life between diagnosis-based subgroups. ‘Impairments in muscle functions’ had the highest prevalence and severity scores in the total sample and diagnosis-based subgroups. Neuromuscular disease-related disabilities showed strong and independent associations with all aspects of health-related quality of life. ‘Impairments in mental functions and pain’ was the most important predictor of health-related quality of life followed by ‘restrictions in participation in life situations’. Conclusions: Although ‘impairment in muscle functions’ is the most prevalent and severe disability, the ‘impairments in mental functions and pain’ have a strong association with health-related quality of life in patients with a neuromuscular disease.Implications for rehabilitationDisease-related disabilities have a strong and independent associations with all aspects of health-related quality of life.Although health-related domains of quality of life are affected by the neuromuscular disease, the general quality of life is quite good.The most prevalent and severe disability in total group and diagnosis-based subgroups is ‘impairments in muscle functions’.The most significant predictor in health-related quality of life is ‘impairments in mental functions and pain’. Disease-related disabilities have a strong and independent associations with all aspects of health-related quality of life. Although health-related domains of quality of life are affected by the neuromuscular disease, the general quality of life is quite good. The most prevalent and severe disability in total group and diagnosis-based subgroups is ‘impairments in muscle functions’. The most significant predictor in health-related quality of life is ‘impairments in mental functions and pain’.

In medical education, student distress is known to hamper learning and professional development. To address this problem, recent studies aimed at helping students cope with stressful situations. Undergraduate students in clinical practice frequently use experiences of surrounding peers to estimate their abilities to master such challenging situations. This use of the experiences of others, known as social comparison, may affect student distress both positively and negatively. To find characteristics of a beneficial use of social comparison, we examined differences in comparison behaviours between students expressing low and high levels of distress. The participants in our study, response rate 93 % (N = 301/321), were all medical students in their first year in clinical practice. They completed the General Health Questionnaire (GHQ-12) to measure distress, and three separate questionnaires to measure: (1) orientation to comparison, (2) motive for comparison, and (3) interpretation of comparison. Differences were analysed using multivariate analysis of variance. Although all students were oriented towards social comparison, the analyses showed that this orientation was less apparent among low-distress students. Besides, the low-distress students were less inclined to use motives indicative for comparisons with peers perceived as performing worse and were less negative in the interpretations of their comparisons. As social comparison is frequently used among all students, we recommend to make them aware of their comparison behaviours and inform them about the pros and cons of the distinguished aspects of the comparison process.

Objectives: To develop a measure that is based on the International Classification of Functioning, Disability and Health (ICF) and reflects the prevalence and severity of disabilities related to neuromuscular disorders, and to evaluate the psychometric properties of this measure.Methods: A preliminary questionnaire was developed, based on the categories of the ICF Core Set for Neuromuscular Diseases. Next a cross-sectional postal survey was carried out among 702 patients (70% response rate) diagnosed with a neuromuscular disease. Finally, psychometric properties were examined.Results: The preliminary Neuromuscular Disease Impact Profile (NMDIP) consisted of 45 items. Factor analysis showed that the NMDIP comprised domains representing 3 ICF-components: 5 factors in the Body Functions component, 2 factors in the Activities component, and 1 factor in the Participation component. Scales showed moderate to good internal consistency (alpha=0.63-0.92) and mean inter-item correlation coefficients (0.38-0.77). Convergent and discriminant validity analysis indicated that the NMDIP measures the impact of neuromuscular disease on physical, mental, and social functioning. The NMDIP discriminates between groups who differ in extent of limitations.Conclusion: The NMDIP is an ICF-based measure that reflects neuromuscular disease-related disabilities. It consists of 36 items divided over 8 scales with satisfactory psychometric properties and 4 single items.

Background: Various feedback characteristics have been suggested to positively influence student learning. It is not clear how these feedback characteristics contribute to students' perceived learning value of feedback in cultures classified low on the cultural dimension of individualism and high on power distance. This study was conducted to validate the influence of five feedback characteristics on students' perceived learning value of feedback in an Indonesian clerkship context.Methods: We asked clerks in Neurology (n = 169) and Internal Medicine (n = 132) to assess on a 5-point Likert scale the learning value of the feedback they received. We asked them to record whether the feedback provider (1) informed the student what went well, (2) mentioned which aspects of performance needed improvement, (3) compared the student's performance to a standard, (4) further explained or demonstrated the correct performance, and (5) prepared an action plan with the student to improve performance. Data were analyzed using multilevel regression.Results: A total of 250 students participated in this study, 131 from Internal Medicine (response rate 99%) and 119 from Neurology (response rate 70%). Of these participants, 225 respondents (44% males, 56% females) completed the form and reported 889 feedback moments. Students perceived feedback as more valuable when the feedback provider mentioned their weaknesses (beta = 0.153, p Conclusions: In Indonesia, we could validate four out of the five characteristics for effective feedback. We argue that our findings relate to culture, in particular to the levels of individualism and power distance. The recognized characteristics of what constitutes effective feedback should be validated across cultures.

Objective: To adapt and to combine the self-report Upper Extremity Functional Index and Lower Extremity Function Scale, for the assessment of disability severity in patients with a neuromuscular disease and to examine its psychometric properties in order to make it suitable for indicating disease severity in neuromuscular diseases. Design: A cross-sectional postal survey study was performed among patients diagnosed with a neuromuscular disease. Methods: Patients completed both adapted extremity function scales, questionnaires for psychometric evaluation, and disease-specific questions. Confirmatory factor analysis was performed, and reliability and validity were examined. Results: Response rate was 70% (n = 702). The Extremity Function Index model with a two-factor structure – for upper and lower extremities – showed an acceptable fit. The Extremity Function Index scales showed good internal consistency (alphas: 0.97–0.98). The known-groups validity test confirmed that Extremity Function Index scales discriminate between categories of “Extent of limitations” and “Quality of Life.” Convergent and divergent validity tests confirmed that Extremity Function Index scales measure the physical impact of neuromuscular diseases. Relative validity tests showed that the Extremity Function Index scales performed well in discriminating between subgroups of patients with increasing “Extent of limitations” compared to concurrent measurement instruments. Conclusion: The Extremity Function Index proved to be a sound and easy to apply self-report disability severity measurement instrument in neuromuscular diseases.Implications for rehabilitationThe Extremity Function Index reflects the functioning of all muscles in the upper and lower extremities involved in activities of daily living.The Extremity Function Index is an easy to administer and patient-friendly disability severity measurement instrument that has the ability to evaluate differences in disability severity between relevant neuromuscular disease subgroups.The Extremity Function Index is a valid and reliable disability severity measurement instrument for neuromuscular diseases. The Extremity Function Index reflects the functioning of all muscles in the upper and lower extremities involved in activities of daily living. The Extremity Function Index is an easy to administer and patient-friendly disability severity measurement instrument that has the ability to evaluate differences in disability severity between relevant neuromuscular disease subgroups. The Extremity Function Index is a valid and reliable disability severity measurement instrument for neuromuscular diseases.