Quantitative whole-body muscle MRI in idiopathic inflammatory myopathies including polymyositis with mitochondrial pathology: indications for a disease spectrum.

OBJECTIVE: Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity. The aim of this study was to compare MRI findings in IIM, including PM-Mito. METHODS: This retrospective analysis included 41 patients (7 PM-Mito, 11 sIBM, 11 PM/ASyS/OLM, 12 IMNM) and 20 healthy controls. Pattern of muscle involvement was assessed by semiquantitative evaluation, while Dixon method was used to quantify muscular fat fraction. RESULTS: The sIBM typical pattern affecting the lower extremities was not found in the majority of PM-Mito-patients. Intramuscular edema in sIBM and PM-Mito was limited to the lower extremities, whereas IMNM and PM/ASyS/OLM showed additional edema in the trunk. Quantitative assessment showed increased fat content in sIBM, with an intramuscular proximo-distal gradient. Similar changes were also found in a few PM-Mito- and PM/ASyS/OLM patients. In sIBM and PM-Mito, mean fat fraction of several muscles correlated with clinical involvement. INTERPRETATION: As MRI findings in patients with PM-Mito relevantly differed from sIBM, the attribution of PM-Mito as sIBM precursor should be critically discussed. Some patients in PM/ASyS/OLM and PM-Mito group showed MR-morphologic features predominantly observed in sIBM, indicative of a spectrum from PM/ASyS/OLM toward sIBM. In some IIM subtypes, MRI may serve as a biomarker of disease severity.

GFPT1-Associated Congenital Myasthenic Syndrome Mimicking a Glycogen Storage Disease - Diagnostic Pitfalls in Myopathology Solved by Next-Generation-Sequencing.

GFPT1-related congenital myasthenic syndrome (CMS) is characterized by progressive limb girdle weakness, and less prominent involvement of facial, bulbar, or respiratory muscles. While tubular aggregates in muscle biopsy are considered highly indicative in GFPT1-associated CMS, excessive glycogen storage has not been described. Here, we report on three affected siblings with limb-girdle myasthenia due to biallelic pathogenic variants in GFPT1: the previously reported missense variant c.41G > A (p.Arg14Gln) and the novel truncating variant c.1265_1268del (p.Phe422TrpfsTer26). Patients showed progressive proximal atrophic muscular weakness with respiratory involvement, and a lethal disease course in adulthood. In the diagnostic workup at that time, muscle biopsy suggested a glycogen storage disease. Initially, Pompe disease was suspected. However, enzymatic activity of acid alpha-glucosidase was normal, and gene panel analysis including 38 genes associated with limb-girdle weakness (GAA included) remained unevocative. Hence, a non-specified glycogen storage myopathy was diagnosed. A decade later, the diagnosis of GFPT1-related CMS was established by genome sequencing. Myopathological reexamination showed pronounced glycogen accumulations, that were exclusively found in denervated muscle fibers. Only single fibers showed very small tubular aggregates, identified in evaluation of serial sections. This family demonstrates how diagnostic pitfalls can be addressed by an integrative approach including broad genetic analysis and re-evaluation of clinical as well as myopathological findings.

Prognosis of patients with pulmonary embolism after rehabilitation.

INTRODUCTION: Pulmonary embolism (PE) is a life-threatening disease; in Germany, therefore, rehabilitation after PE is recommended in patients with intermediate- and high-risk PE. However, no prospective data on PE after inpatient rehabilitation have been published so far. PATIENTS AND METHODS: For this monocentric study, 70 patients with PE were prospectively recruited between November 2013 and November 2014 after giving written informed consent. This study was approved by the ethics committee of the Medical Association of Saxony-Anhalt. Inclusion criteria were as follows: age ≥18 years and a stay at the Paracelsus-Harz Clinic in Bad Suderode, Germany, with the main indication of PE. During the hospital stay, history-relevant medical data and diagnostic findings were collected and documented. Furthermore, we recorded whether patients were rehospitalized or died during the treatment period in the rehabilitation clinic or during the 12-month follow-up. RESULTS: The mean age was 64.5 ± 13.0 years, the mean body mass index (BMI) was 30.4 ± 6.0 kg/m2, and 54.3% were women. During rehabilitation, two patients (3.9%) were transferred to a primary care hospital; no patient died. However, four patients died (5.7%) in the 12-month follow-up period. A total of 20 patients were hospitalized in the 12-month follow-up period (hospitalization rate during the 12-month follow-up period: 28.6%). Of these 20 patients, one patient was rehospitalized with a newly diagnosed PE (1.4%) and two patients were rehospitalized for bleeding events (2.8%). CONCLUSION: PE is a life-threatening disease, and therefore it seems reasonable to recommend rehabilitation at least in patients with an intermediate- or high-risk PE. In this study, death and other serious event rates were low during the in-hospital rehabilitation and in the 12-month follow-up period, which underlined the safety and importance of a standardized rehabilitation program after survived PE.