Oral ribose supplementation in dystroglycanopathy: A single case study.

Three forms of muscular dystrophy-dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain-containing protein (ISPD), fukutin-related protein (FKRP), and fukutin (FKTN) genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O-glycan of alpha-dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate-ribitol (CDP-ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous FKRP mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP-ribitol levels with 18 g of ribose supplementation (p < 0.001). Although objective improvement in clinical and patient-reported outcome measures was not observed, the patient reported subjective improvement of muscle strength, fatigue, and pain. This case study indicates that ribose supplementation in patients with dystroglycanopathy is safe and highlights the importance for future studies regarding its potential effects.

Perioperative Care for Patients with Neuromuscular Disorders in the Netherlands - A Questionnaire Study Among Anaesthesiologists, Neurologists and Clinical Geneticists.

BACKGROUND: Patients with neuromuscular disorders are at increased risk of suffering perioperative complications. Current knowledge concerning this topic is based on small retrospective studies and expert opinion. Therefore, an individualized multidisciplinary approach to perioperative anaesthesia planning is invaluable to anticipate difficulties and to optimize outcomes. OBJECTIVE: To evaluate current practice regarding preoperative counselling and perioperative care of neuromuscular patients, with the aim to facilitate standardization and improvement of perioperative care for neuromuscular patients. METHODS: A questionnaire-based cross-sectional, observational study was conducted between July, 1st 2020 and December, 31st, 2020 in Dutch anaesthesia, neurology and clinical genetics departments. Main outcome measures were 1.) frequency of consultation requests for neuromuscular patients prior to surgery, 2.) current practice, educational activities and departmental approach to this topic and 3.) preoperative counselling of neuromuscular patients. RESULTS: A total of 83 departments participated. Consultations for a neuromuscular patient scheduled for anaesthesia were requested from anaesthesia and neurology department only infrequently. Local guidelines concerning perioperative care of neuromuscular patients were available in 36.4% of the participating departments. Quality of specific training for residents and staff anaesthetists/neurologists covering perioperative care of neuromuscular patients was rated as 'very good' or 'good' by 42.9%. Neuromuscular patients scheduled for surgery were 'always' or 'often' discussed in multidisciplinary meetings involving anaesthesiologists and neurologists in 20.8% of the participating departments. CONCLUSION: Perioperative care for neuromuscular patients in the Netherlands is highly variable and might benefit from guidelines, education of health care professionals and multidisciplinary meetings between anaesthesiologists and neurologists on a regular basis.

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Health-related quality of life in Dutch adult survivors of childhood cancer: A nation-wide cohort study.

AIM: To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL. METHODS: Adult CCS (age >18, diagnosed <18, ≥5 years since diagnosis) from the Dutch LATER registry completed the Medical Outcome Study Short Form 36 (SF-36) to measure HRQOL and provided sociodemographic characteristics. Age-adjusted mean SF-36 scale scores of CCS were compared to the Dutch general population for men and women separately using t-tests, with effect size d. Multivariate logistic regression models were built to identify sociodemographic and cancer-related risk factors for impaired physical and mental HRQOL. RESULTS: Both male and female CCS (N = 2301, mean age = 35.4 years, 49.6% female) reported significantly (p ≤ .005) worse HRQOL than the general population on almost all scales of the SF-36 (-.11 ≤ d ≤ -.56). Largest differences were found on vitality and general health perceptions. Significant risk factors (p ≤ .05) for impaired physical HRQOL were female sex, older age at diagnosis, not having a partner, low educational attainment, disease recurrence and exposure to radiotherapy, specifically to lower extremity radiation. Odds ratios (ORs) ranged from 1.6 to 3.7. Significant risk factors for impaired mental HRQOL were age 26-35 years, male sex, not having a partner and low educational attainment. ORs ranged from 1.3 to 2.0. CONCLUSION: Adult CCS had worse HRQOL than the general population. CCS most at risk were those with low educational attainment and without a partner. Adult CCS could benefit from routine surveillance of their HRQOL. Special attention for CCS' vitality and health perceptions and beliefs is warranted.

Treatment-related fertility impairment in long-term female childhood, adolescent and young adult cancer survivors: investigating dose-effect relationships in a European case-control study (PanCareLIFE).

STUDY QUESTION: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors? SUMMARY ANSWER: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. WHAT IS KNOWN ALREADY: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce. STUDY DESIGN, SIZE, DURATION: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites. MAIN RESULTS AND THE ROLE OF CHANCE: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. LIMITATIONS, REASONS FOR CAUTION: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results. WIDER IMPLICATIONS OF THE FINDINGS: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired. STUDY FUNDING/COMPETING INTEREST(S): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests. TRIAL REGISTRATION NUMBER: n/a.

Randomized trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: High peak serum immunoglobulin G (IgG) levels may not be needed for maintenance intravenous immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and such high levels may cause side effects. More frequent lower dosing may lead to more stable IgG levels and higher trough levels, which might improve efficacy. The aim of this trial is to investigate whether high frequent low dosage IVIg treatment is more effective than low frequent high dosage IVIg treatment. METHODS: In this randomized placebo-controlled crossover trial, we included patients with CIDP proven to be IVIg-dependent and receiving an individually established stable dose and interval of IVIg maintenance treatment. In the control arm, patients received their individual IVIg dose and interval followed by a placebo infusion at half the interval. In the intervention arm, patients received half their individual dose at half the interval. After a wash-out phase patients crossed over. The primary outcome measure was handgrip strength (assessed using a Martin Vigorimeter). Secondary outcome indicators were health-related quality of life (36-item Short-Form Health Survey), disability (Inflammatory Rasch-built Overall Disability Scale), fatigue (Rasch-built Fatigue Severity Scale) and side effects. RESULTS: Twenty-five patients were included and were treated at baseline with individually adjusted dosages of IVIg ranging from 20 to 80 g and intervals ranging from 14 to 35 days. Three participants did not complete the trial; the main analysis was therefore based on the 22 patients completing both treatment periods. There was no significant difference in handgrip strength change from baseline between the two treatment regimens (coefficient -2.71, 95% CI -5.4, 0.01). Furthermore, there were no significant differences in any of the secondary outcomes or side effects. CONCLUSIONS: More frequent lower dosing does not further improve the efficacy of IVIg in stable IVIg-dependent CIDP and does not result in fewer side effects.

New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.

Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3-6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.

Diagnostic value of additional histopathological fascia examination in idiopathic inflammatory myopathies.

BACKGROUND AND PURPOSE: Correct diagnosis of idiopathic inflammatory myopathies (IIM) may prevent harm from both lack of treatment in IIM patients and unnecessary treatment in non-IIM patients. However, it is unknown whether additional histopathological fascia examination may contribute to diagnosing IIM. METHODS: Thirty-two magnetic resonance imaging guided en bloc biopsies from patients diagnosed with IIM (except inclusion body myositis) from 2010 to 2017 were reviewed: dermatomyositis (DM) (n = 6), non-specific/overlap myositis (NM/OM) (n = 11), immune-mediated necrotizing myopathy (n = 12) and anti-synthetase syndrome (n = 3). Muscle biopsy specimens were examined according to the 2004 European Neuromuscular Centre (ENMC) criteria. Fascia was subsequently examined for the presence of lymphocytic infiltrates. Isolated fascia involvement was defined as the presence of lymphocytic infiltrates in the fascia/epimysium on histopathology in the absence of any ENMC muscle histopathology/immunohistochemistry criteria. RESULTS: One patient with DM (17%) and one patient with NM/OM (9%) had isolated fascia involvement. One patient with immune-mediated necrotizing myopathy (8%) and one patient with anti-synthetase syndrome (33%) had fascia involvement, albeit in combination with muscle involvement. CONCLUSION: Histopathological fascia examination may contribute to early diagnosis of DM and NM/OM in a small proportion of patients.

The influence of genetic variation on late toxicities in childhood cancer survivors: A review.

INTRODUCTION: The variability in late toxicities among childhood cancer survivors (CCS) is only partially explained by treatment and baseline patient characteristics. Inter-individual variability in the association between treatment exposure and risk of late toxicity suggests that genetic variation possibly modifies this association. We reviewed the available literature on genetic susceptibility of late toxicity after childhood cancer treatment related to components of metabolic syndrome, bone mineral density, gonadal impairment and hearing impairment. METHODS: A systematic literature search was performed, using Embase, Cochrane Library, Google Scholar, MEDLINE, and Web of Science databases. Eligible publications included all English language reports of candidate gene studies and genome wide association studies (GWAS) that aimed to identify genetic risk factors associated with the four late toxicities, defined as toxicity present after end of treatment. RESULTS: Twenty-seven articles were identified, including 26 candidate gene studies: metabolic syndrome (n = 6); BMD (n = 6); gonadal impairment (n = 2); hearing impairment (n = 12) and one GWAS (metabolic syndrome). Eighty percent of the genetic studies on late toxicity after childhood cancer had relatively small sample sizes (n < 200), leading to insufficient power, and lacked adjustment for multiple comparisons. Only four (4/26 = 15%) candidate gene studies had their findings validated in independent replication cohorts as part of their own report. CONCLUSION: Genetic susceptibility associations are not consistent or not replicated and therefore, currently no evidence-based recommendations can be made for hearing impairment, gonadal impairment, bone mineral density impairment and metabolic syndrome in CCS. To advance knowledge related to genetic variation influencing late toxicities among CCS, future studies need adequate power, independent cohorts for replication, harmonization of disease outcomes and sample collections, and (international) collaboration.

[Myositis: more than a muscle disease]. / Myositis is meer dan een spierziekte.

Idiopathic inflammatory myopathy (IIM), commonly referred to as "myositis", is a rare but treatable auto-immune disease that is often misdiagnosed or diagnosed after significant delay. Using three clinical case reports as introductory examples, an overview is given - and pitfalls are discussed - of the diagnosis and treatment of myositis. Disease features are often extra-muscular in nature, may vary considerably between patients, and are frequently non-specific. Myositis-related morbidity is high and myositis can be fatal, mainly due to cancer and interstitial lung disease. As such, we stress the importance of early recognition of this severe disease and timely referral of a patient with a (suspected) IIM to a multidisciplinary team for optimal diagnosis and disease management.

Longitudinal follow-up in female Childhood Cancer Survivors: no signs of accelerated ovarian function loss.

STUDY QUESTION: Is the long-term decline of ovarian function, as reflected by a decrease in serum anti-Müllerian hormone (AMH) concentration, accelerated over time in female childhood cancer survivors (CCS) as compared to healthy women of the same age? SUMMARY ANSWER: The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls. WHAT IS KNOWN ALREADY: Gonadal function is compromised in female CCS treated with chemotherapy and/or radiation therapy. Ovarian function is most compromised in survivors treated with total body irradiation, abdominal or pelvic irradiation, stem cell transplantation or high doses of alkylating agents. STUDY DESIGN SIZE, DURATION: Longitudinal single-centre cohort study in 192 CCS in Rotterdam, The Netherlands, between 2001 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH levels of 192 adult female CCS were assessed, at least five years after cessation of treatment and at a follow-up visit with a median of 3.2 years (range: 2.1-6.0) later and were compared to the age-based P50 of AMH in healthy controls. MAIN RESULTS AND THE ROLE OF CHANCE: Median AMH levels were below the P50 at both visit 1 (-0.59 µg/L) and at visit 2 (-0.22 µg/L). In women with a sustained ovarian function (AMH > 1.0 µg/L), the decline in AMH is similar to that in the normal population (difference in decline per year: -0.07 µg/L (range: -2.86 to 4.92), P  = 0.75). None of the treatment modalities was correlated with a significant acceleration of decline of AMH per year. LIMITATIONS REASONS FOR CAUTION: We selected CCS that visited our late effect outpatient clinic and who had two AMH levels available. It is conceivable that women without any apparent late effects of treatment as well as women with extreme late effects, which might be the ones with the largest impact on ovarian function, could be more likely to be lost to follow-up. However, general characteristics did not differ between the included and excluded patients. WIDER IMPLICATIONS OF THE FINDINGS: While prospective longitudinal research is required to strengthen our findings, they may help physicians to counsel female CCS about their expected reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: A.L.F.v.d.K., M.M.v.d.H.-E. and S.M.F.P. are supported by FP7-PanCare LIFE. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. The other authors have no conflicts of interest to declare.

Muscle imaging in inherited and acquired muscle diseases.

In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders.

Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume.

BACKGROUND AND PURPOSE: Thirty per cent of amyotrophic lateral sclerosis (ALS) patients have non-motor symptoms, including executive and memory deficits. The in vivo anatomical basis of memory deficits in ALS has not been elucidated. In this observational study, brain atrophy in relation to memory function was investigated in ALS patients and controls. METHODS: Twenty-six ALS patients without dementia and 21 healthy volunteers matched for gender, age and education level underwent comprehensive neuropsychological evaluation and T1- and T2-weighted 3 T magnetic resonance imaging scanning of the brain. Grey and white matter brain volumes were analysed using voxel-based morphometry and age related white matter changes were assessed. The most frequently abnormal memory test (<2 SD below normative data corrected for age, gender and education) was correlated with regional brain volume variations by multiple regression analyses with age, gender and total grey matter volumes as covariates. RESULTS: Immediate and delayed story recall scores were abnormal in 23% of ALS patients and correlated to bilateral hippocampus grey matter volume (r = 0.52 for both memory tests; P < 0.05; corrected for age, gender and total grey matter volume). This correlation was not found in healthy controls with similar age, education, anxiety and depression levels and white matter changes. CONCLUSIONS: Prose memory impairment is a frequent finding in this cohort and is associated with hippocampus volume in ALS patients without dementia. These findings complement previous hippocampus changes in imaging studies in ALS and suggest involvement of the hippocampus in cognitive dysfunction of ALS.

Classification of daily mental status in critically ill patients for research purposes.

PURPOSE: The purpose of this study is to develop a reliable tool for daily mental status classification in intensive care unit (ICU) patients for research purposes. Secondly, to identify patients with single, 1-day episodes of delirium and to compare them with patients having more delirium days or episodes. PATIENTS AND METHODS: A 5-step algorithm was designed, which includes Richmond Agitation Sedation Scale and Confusion Assessment Method for the ICU scores from bedside nurses, initiation of delirium treatment, chart review, and the Confusion Assessment Method for the ICU administered by researchers. This algorithm was validated against a reference standard of delirium experts. Subsequently, a cohort study was performed in patients admitted to a mixed ICU. RESULTS: In 65 paired observations, the algorithm had 0.75 sensitivity and 0.85 specificity. Applying the algorithm, interobserver agreement was high with mean Fleiss κ of 0.94 (5 raters) and 0.97 (4 raters). In the cohort study, 1112 patients were included of whom 535 (48%) became delirious. Single, 1-day episodes occurred in 43% of the delirious patients, whom were characterized by lower age compared with those with more delirium days. CONCLUSIONS: The algorithm for daily mental status classification seems to be a valid tool. In a substantial proportion of patients, delirium occurs only once during ICU admission lasting only 1 day.

Opportunities and methodological challenges in EEG and MEG resting state functional brain network research.

Electroencephalogram (EEG) and magnetoencephalogram (MEG) recordings during resting state are increasingly used to study functional connectivity and network topology. Moreover, the number of different analysis approaches is expanding along with the rising interest in this research area. The comparison between studies can therefore be challenging and discussion is needed to underscore methodological opportunities and pitfalls in functional connectivity and network studies. In this overview we discuss methodological considerations throughout the analysis pipeline of recording and analyzing resting state EEG and MEG data, with a focus on functional connectivity and network analysis. We summarize current common practices with their advantages and disadvantages; provide practical tips, and suggestions for future research. Finally, we discuss how methodological choices in resting state research can affect the construction of functional networks. When taking advantage of current best practices and avoid the most obvious pitfalls, functional connectivity and network studies can be improved and enable a more accurate interpretation and comparison between studies.

Rhabdomyolysis: review of the literature.

Rhabdomyolysis is a serious and potentially life threatening condition. Although consensus criteria for rhabdomyolysis is lacking, a reasonable definition is elevation of serum creatine kinase activity of at least 10 times the upper limit of normal followed by a rapid decrease of the sCK level to (near) normal values. The clinical presentation can vary widely, classical features are myalgia, weakness and pigmenturia. However, this classic triad is seen in less than 10% of patients. Acute renal failure due to acute tubular necrosis as a result of mechanical obstruction by myoglobin is the most common complication, in particular if sCK is >16.000 IU/l, which may be as high as 100,000 IU/l. Mortality rate is approximately 10% and significantly higher in patients with acute renal failure. Timely recognition of rhabdomyolysis is key for treatment. In the acute phase, treatment should be aimed at preserving renal function, resolving compartment syndrome, restoring metabolic derangements, and volume replacement. Most patients experience only one episode of rhabdomyolysis, mostly by substance abuse, medication, trauma or epileptic seizures. In case of recurrent rhabdomyolysis, a history of exercise intolerance or a positive family history for neuromuscular disorders, further investigations are needed to identify the underlying, often genetic, disorder. We propose a diagnostic algorithm for use in clinical practice.

Reliability of the walking energy cost test and the six-minute walk test in boys with Duchenne muscular dystrophy.

The walking energy cost test (WECT) is a useful tool when measuring ambulatory function in children with motor disorders. However, data on the reliability of this test in Duchenne muscular dystrophy (DMD) is not available. In this study we established the reliability of the WECT and the commonly used six-minute walk test (6MWT) in 19 boys with DMD, aged 6-12years. Participants performed the WECT and 6MWT twice within three weeks. Reliability was determined for walking distance (D, m) and gross energy cost (EC, Jkg(-1)m(-1)), using the intraclass correlation coefficient (ICC2,1) and smallest detectable change (SDC). Reliability for walking distance was good, with an ICC of 0.92 [95% CI: 0.81-0.97] and 0.83 [CI: 0.53-0.94] for the 6MWT and WECT, respectively, and an ICC of 0.85 [CI: 0.64-0.94] for gross EC. SDCs were 12.2% for D6MWT, 12.7% for DWECT and 18.5% for gross EC. In conclusion, in young boys with DMD, the reliability of both the WECT and 6MWT for assessing walking distance is adequate. Gross EC, as assessed with the WECT is also reliable and sufficiently sensitive to detect change in walking strain following interventions at group level.

Idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs), except for sporadic inclusion body myositis (sIBM), present with subacute symmetrical weakness of the limb girdle muscles, an elevated serum creatine kinase activity, and inflammatory cells in the muscle biopsy (necrotizing autoimmune myopathy being an exception). In dermatomyositis, additional skin abnormalities are found. IIMs are nowadays subclassified into the following categories: (1) dermatomyositis (DM), including (1a) classic dermatomyositis, which may be associated with connective tissue disorders (CTDs) and malignancy, (1b) juvenile dermatomyositis, and (1c) clinical amyopathic dermatomyositis; (2) polymyositis (PM) encompassing (2a) classical PM and (2b) nonspecific or overlap myositis, associated with CTD; (3) autoimmune necrotizing myopathy, associated with malignancy, statin use and CTD; and (4) sporadic IBM, sometimes associated with CTDs. These conditions result from chronic immune activation after exposure to environmental risk factors in individuals with a predisposing genetic background. A strong association of autoantibodies with distinct clinical phenotypes and prognosis is found in patients with myositis. Inflammatory myopathies, sporadic IBM excluded, are amenable to immunosuppressive and immunomodulation therapies. The prognosis of IIM is not well known since long-term outcome and prognostic factors vary widely. Disease-related mortality rates in PM and DM are at least 10%. In DM mortality is attributed to cancer and pulmonary complications. Juvenile dermatomyositis has a low mortality rate. Because chronic immunosuppressive therapy is associated with significant side-effects, and many patients remain (partially) refractory to treatment, novel therapeutic agents that are safe and effective are needed.