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Context: Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing's syndrome (CS). Its long-term outcome is largely unknown., Objective: To evaluate long-term muscle function following the remission of endogenous CS., Study Design: Observational longitudinal cohort study., Setting: Tertiary care hospitals and a specialized outpatient clinic., Patients: As part of the prospective multicenter German Cushing's Registry, we assessed muscle strength in patients with overt endogenous CS. We studied the patients at the time of diagnosis (n = 88), after 6 months (n = 69), and thereafter annually, following surgical remission over a period of up to 4 years (1 year: n = 55; 2 years: n = 34; 3 years: n = 29; 4 years: n = 22). Muscle function was evaluated by hand grip strength and by chair rising test., Results: Grip strength was decreased to 83% of normal controls (100%) at the time of diagnosis. It further decreased to 71% after 6 months in remission (P ≤ 0.001) and showed no improvement during further follow-up compared with baseline. Chair rising test performance improved initially (8 seconds at baseline vs 7 seconds after 6 months, P = 0.004) but remained at this reduced level thereafter (7 seconds after 3 years vs 5 seconds in controls, P = 0.038). In multivariate analysis, we identified, as predictors for long-term muscle dysfunction, age, waist-to-hip ratio, and hemoglobin A1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life., Conclusion: This study shows that CS-associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting., (© Endocrine Society 2020.)

Background: Early-onset myopathies are a heterogeneous group of neuromuscular diseases with broad clinical, genetic and histopathological overlap. The diagnostic approach has considerably changed since high throughput genetic methods (next generation sequencing, NGS) became available., Objective: We present diagnostic subgroups in a single neuromuscular referral center and describe an algorithm for the diagnostic work-up., Methods: The diagnostic approach of 98 index patients was retrospectively analysed. In 56 cases targeted sequencing of a known gene was performed, in 44 patients NGS was performed using large muscle specific panels, and in 12 individuals whole exome sequencing (WES) was undertaken. One patient was diagnosed via array CGH. Clinical features of all patients are provided., Results: The final diagnosis could be found in 63 out of 98 patients (64%) with molecular genetic analysis. In 55% targeted gene sequencing could establish the genetic diagnosis. However, this rate largely depended on the presence of distinct histological or clinical features. NGS (large myopathy-related panels and WES) revealed genetic diagnosis in 58.5% (52% and 67%, respectively). The genes detected by WES in our cohort of patients were all covered by the panels. Based on our findings we propose an algorithm for a practical diagnostic approach.Prevalences:MTM1- and LAMA2-patients are the two biggest subgroups, followed by SEPN1-, RYR1- and Collagen VI-related diseases. 31% of genetically confirmed cases represents a group with overlap between "congenital myopathies (CM)" and "congenital muscular dystrophies (CMD)". In 36% of the patients a specific genetic diagnosis could not be assigned., Conclusions: A final diagnosis can be confirmed by high throughput genetic analysis in 58.5% of the cases, which is a higher rate than reported in the literature for muscle biopsy and should in many cases be considered as a first diagnostic tool. NGS cannot replace neuromuscular expertise and a close discussion with the geneticists on NGS is mandatory. Targeted candidate gene sequencing still plays a role in selected cases with highly suspicious clinical or histological features. There is a relevant clinical and genetic overlap between the entities CM and CMD.

A frequent cause of weaning failure and the resultant long-term artificial ventilation is the generalized weakness syndrome in the sense of critical illness polyneuropathy or polymyopathy. However, hardly any information is presently available regarding the necessary intensity of the diagnostic workup for reaching or excluding a diagnosis with certainty in the neurological examination or regarding the additional diagnostic value of electrophysiological studies in patients receiving long-term acute care suspected of having critical illness polyneuropathy and polymyopathy. Therefore, the goal of this investigation was to address these questions. A total of 280 patients with complicated weaning were included in the study. All patients underwent clinical examination by a specialist in neurology and electrophysiological workup performed by another specialist. Among the patients studied, the greatest possible certainty of the diagnosis (positive predictive value) of the clinical examination was 97.9% [95% confidence interval (CI) 69.4-99.9] and the best certainty of excluding the diagnosis (negative predictive value) was 88.9% (95% CI 82.7-93.0). Thus, in difficult-to-wean patients who were considered to probably have the diagnosis of critical illness polyneuropathy or polymyopathy as assessed by a specialist, little additional information is gained from an electrophysiological study, which is hence dispensable in these cases.

Background: New therapeutic strategies in muscular dystrophies will make a difference in prognosis only if they are begun early in the course of the disease. Therefore, we investigated factors that influence the time to diagnosis in muscle dystrophy patients., Methods: A sample of 101 patients (mean age 49 years; range 19-80; 44% women) with diagnosed muscle dystrophies from neurological practices and the neuromuscular specialty clinic in Berlin, Germany, was invited to participate. Time from first consultation to diagnosis, subspecialty of physician, and sociodemographic data were assessed with self-report questionnaires. The association between time to diagnosis and potential predictors (subspecialty of initially consulted physician, diagnoses, gender, and age at onset) was modeled with linear regression analysis., Results: The mean time span between first health-care contact and diagnosis was 4.3 years (median 1). The diagnostic delay was significantly longer if patients were initially seen by a non-neurological specialist compared to a general practitioner (5.2 vs. 3.5 years, p = 0.047). Other factors that were independently associated with diagnostic delay were female gender and inherited muscle disease., Conclusion: Action to improve clinical awareness of muscle diseases in non-neurological specialists is needed.

Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. It is questionable, whether there is a strong association of the sequence with autism spectrum disorders (ASDs) as suggested in some earlier case reports and studies. Twenty-two participants with Möbius sequence aged 6-16 years followed a request of the German Moebius foundation to participate in a nationwide study. All patients had a physical examination and intelligence testing. Primary caregivers were asked to complete two screening measures of ASD (Behaviour and Communication Questionnaire, VSK; Marburger Asperger's Syndrome Rating Scale, MBAS). For those who reached the cut-off for ASD and/or showed behavioural aspects indicative of ASDs during IQ testing and/or physical examination, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and Kinder-DIPS) were administered. Minimal diagnostic criteria for Möbius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Three boys (one of them mentally retarded) out of 22 participants (12 males and 10 females) were found suspicious of ASD by screening, but none of them fulfilled diagnostic criteria of ASD on a clinical consensus conference. Therefore, ASDs seem to be not as frequent as reported in previous studies on patients with Möbius sequence., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: Musculoskeletal complaints are very common in primary care settings. Lipid-lowering drugs are one of several causes of musculoskeletal symptoms. However, data showing an association of lipid-lowering drug therapy and increased odds of musculoskeletal complaints in primary care patients are lacking., Objective: To investigate the association between statin use and the reporting of muscular complaints by patients and simultaneously control for several known factors of musculoskeletal complaints., Methods: In a cross-sectional study with 1031 consecutive patients (>50 years of age) in 26 offices of GPs, two investigators collected the data from the office files and by interviewing the patients. A logistic regression model was used to identify variables affecting the odds of muscular symptoms., Results: The prevalence of lipid-lowering drug prescription was 23% (n = 239) and that of muscular complaints was 40% (n = 411). In all, 44% (n = 106) of the patients with lipid-lowering drug prescription had muscular complaints compared to 39% (n = 305) of the patients without lipid-lowering drug therapy. Statin prescription and 10 variables remained in the final model. Statin prescription is associated with a 1.5-fold odds of musculoskeletal complaints compared to non-prescription {odds ratio [OR] = 1.5 [95% confidence interval (CI), 1.1-2.0], P = 0.02}., Conclusion: Having a statin prescription appears to be an independent factor associated with musculoskeletal symptoms in primary care settings. Statin use may be more often associated with musculoskeletal complaints than previously assumed.

Objective: Critical illness polyneuropathy/myopathy (CIP/CIM) is frequently described in critically ill patients who survive severe sepsis. Clinically relevant paresis is major symptom of CIP/CIM. We aimed at determining risk factors and diagnostic value of electrophysiologic testing for CIP/CIM in patients with acute respiratory distress syndrome (ARDS)., Design: Single-center, retrospective analysis, using charts., Setting: University medical center., Patients: Fifty consecutive ARDS patients in our intensive care unit., Interventions: Patient characteristics and clinical course were analyzed. All patients received early electrophysiologic testing. CIP/CIM was diagnosed by the presence of clinical relevant paresis., Measurements and Main Results: Clinically relevant paresis was confirmed in 27 ARDS patients (60%), whereas in 18 patients no paresis was determined (controls); five patients died before clinical assessment of paresis was feasible. Patients with paresis were older, had more days on mechanical ventilation, and had increased intensive care unit length of stay compared with controls. Patients who developed paresis had elevated daily peak blood glucose levels during 28 days of intensive care unit treatment: 166 (134, 200) mg/dL in CIP/CIM patients vs. 144 (132, 161) mg/dL in controls (median, quartiles). Twenty-five of 27 patients with paresis revealed reduced motor unit potentials, fibrillation potentials, or positive sharp waves on early electrophysiologic testing indicating CIP/CIM, whereas 16 of 18 control patients did not., Conclusions: In ARDS patients, paresis is a frequent complication causing prolonged mechanical ventilation and intensive care unit length of stay. An association between hyperglycemia and CIP/CIM has been found. However, since this is a retrospective survey, a causal relation is not clearly supported. In this study, the use of early electrophysiologic testing in ARDS patients was a valuable diagnostic tool for detecting CIP/CIM.

Diabetic muscle infarction (DMI) is a largely unfamiliar disease. It affects mainly patients around 40 years of age with long-standing diabetes and concomitant end-organ complications. The symptoms represent a classic pattern of a musculoskeletal disease with muscle pain without trauma, swelling, and functional impairment. Although its short-term prognosis is good, with improvement of the symptoms over weeks or months under analgesia and rest, a high recurrence rate of up to 60% can be observed. Additionaly, the long-term survival of patients after DMI is reduced mostly due to major vascular complications. Since many diabetic patients are in orthopedic care for musculoskeletal disorders, the orthopedic surgeon should be aware of this disease to avoid unnecessary invasive diagnostic procedures and initiate suitable therapy. Furthermore, a better knowledge of the disease could lead to definite conclusions regarding its real incidence and aid in establishing new therapeutic measures for prophylaxis and better long-term survival.