No abstract

There is no effective treatment available for facioscapulohumeral muscular dystrophy type 1 (FSHD1), but emerging therapies are under way that call for a better understanding of natural history in this condition. In this prospective, longitudinal study, we used quantitative MRI to assess yearly disease progression in patients with FSHD1. Ambulatory patients with confirmed diagnosis of FSHD1 (25/20 men/women, age 20-75 years, FSHD score: 0-12) were tested with 359-560-day interval between tests. Using the MRI Dixon technique, muscle fat replacement was evaluated in paraspinal, thigh, and calf muscles. Changes were compared with those in FSHD score, muscle strength (hand-held dynamometry), 6-minute-walk-distance, 14-step-stair-test, and 5-time-sit-to-stand-test. Composite absolute fat fraction of all assessed muscles increased by 0.036 (CI 0.026-0.046, P < 0.001), with increases in all measured muscle groups. The clinical severity FSHD score worsened (10%, P < 0.05), muscle strength decreased over the hip (8%), neck (8%), and back (17%) (P < 0.05), but other strength measures, 6-minute-walk-distance, 5-times-sit-to-stand-test, and 14-step-stair-test were unchanged. Changes in muscle strength, FSHD score, and fat fraction did not correlate. This first study to systemically monitor quantitative fat replacement longitudinally in FSHD1 shows that MRI provides an objective measure of disease progression, often before changes can be appreciated in strength and functional tests. The study indicates that quantitative MRI can be a helpful end-point in follow-up and therapeutic trials of patients with FSHD1.

This study provides Class I evidence that bezafibrate 200 mg 3 times daily is ineffective in improving changes in FAO and HR during exercise in adults with CPT II and VLCAD deficiencies.

Mexiletine is the only drug with proven effect for treatment of non-dystrophic myotonia, but mexiletine is expensive, has limited availability and several side effects. There is therefore a need to identify other pharmacological compounds that can alleviate myotonia in non-dystrophic myotonias. Like mexiletine, lamotrigine is a sodium channel blocker, but unlike mexiletine, lamotrigine is available, inexpensive, and well tolerated. We investigated the potential of using lamotrigine for treatment of myotonia in patients with non-dystrophic myotonias. In this, randomized double-blind, placebo-controlled, two-period cross-over study, we included adult outpatients recruited from all of Denmark with clinical myotonia and genetically confirmed myotonia congenita and paramyotonia congenita for investigation at the Copenhagen Neuromuscular Center. A pharmacy produced the medication and placebo, and randomized patients in blocks of 10. Participants and investigators were all blinded to treatment until the end of the trial. In two 8-week periods, oral lamotrigine or placebo capsules were provided once daily, with increasing doses (from 25 mg, 50 mg, 150 mg to 300 mg) every second week. The primary outcome was a severity score of myotonia, the Myotonic Behaviour Scale ranging from asymptomatic (score 1) to invalidating myotonia (score 6), reported by the participants during Weeks 0 and 8 in each treatment period. Clinical myotonia was also measured and side effects were monitored. The study was registered at ClinicalTrials.gov (NCT02159963) and EudraCT (2013-003309-24). We included 26 patients (10 females, 16 males, age: 19-74 years) from 13 November 2013 to 6 July 2015. Twenty-two completed the entire study. One patient withdrew due to an allergic reaction to lamotrigine. Three patients withdrew for reasons not related to the trial intervention. The Myotonic Behaviour Scale at baseline was 3.2 ± 1.1, which changed after treatment with lamotrigine by 1.3 ± 0.2 scores (P < 0.001), but not with placebo (0.2 ± 0.1 scores, P = 0.4). The estimated effect size was 1.0 ± 0.2 (95% confidence interval = 0.5-1.5, P < 0.001, n = 22). The standardized effect size of lamotrigine was 1.5 (confidence interval: 1.2-1.8). Number needed to treat was 2.6 (P = 0.006, n = 26). No adverse or unsuspected event occurred. Common side effects occurred in both treatment groups; number needed to harm was 5.2 (P = 0.11, n = 26). Lamotrigine effectively reduced myotonia, emphasized by consistency between effects on patient-related outcomes and objective outcomes. The frequency of side effects was acceptable. Considering this and the high availability and low cost of the drug, we suggest that lamotrigine should be used as the first line of treatment for myotonia in treatment-naive patients with non-dystrophic myotonias.

No abstract

This study provides Class II evidence that regular aerobic training with or without postexercise protein-carbohydrate supplementation improves fitness and workload in patients with FSHD.

Frequent, moderate-intensity aerobic conditioning is of little beneficial effect in patients with spinal and bulbar muscular atrophy (SBMA). High levels of plasma creatine kinase and muscle regeneration indicate a primary myopathic affection, which, in parallel with the motor neuron deficiency, may attenuate the response to exercise training in patients with SBMA.

Markers of types I and III collagen turnover were measured in serial blood samples in 16 patients with a Colles' fracture. The collagen markers were the carboxy-terminal extension peptide of type I procollagen (PICP) and the amino-terminal extension peptide of type III procollagen (PIIINP). Significant increases were found of PIIINP within 1 week and of PICP within 2 weeks. This sequential appearance of PIIINP and PICP was found to be in agreement with the appearance of types III and I collagen during early fracture healing as demonstrated in previous animal experimental studies. PICP had levelled off after 9 months, whereas PIIINP remained elevated. Osteocalcin, a serum marker of osteoblast activity, increased within 1 week and levelled off after 9 months. Correlations between the change in osteocalcin and those in PICP and PIIINP, respectively, were weak. These new biochemical markers may prove relevant as non-invasive markers of normal and pathological fracture healing in humans.