Circulating small RNA signatures differentiate accurately the subtypes of muscular dystrophies: small-RNA next-generation sequencing analytics and functional insights

Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is an increasing interest for the development of novel non-invasive biomarkers for the diagnosis and monitoring of these diseases. miRNAs are small RNA molecules characterized by high stability in blood thus making them ideal biomarker candidates for various diseases. In this study, we present the first genome-wide next-generation small RNA sequencing in serum samples of five different types of muscular dystrophy patients and healthy individuals. We identified many small RNAs including miRNAs, lncRNAs, tRNAs, snoRNAs and snRNAs, that differentially discriminate the muscular dystrophy patients from the healthy individuals. Further analysis of the identified miRNAs showed that some miRNAs can distinguish the muscular dystrophy patients from controls and other miRNAs are specific to the type of muscular dystrophy. Bioinformatics analysis of the target genes for the most significant miRNAs and the biological role of these genes revealed different pathways that the dysregulated miRNAs are involved in each type of muscular dystrophy investigated. In conclusion, this study shows unique signatures of small RNAs circulating in five types of muscular dystrophy patients and provides a useful resource for future studies for the development of miRNA biomarkers in muscular dystrophies and for their involvement in the pathogenesis of the disorders

Painful ophthalmoplegia: The role of imaging and steroid response in the acute and subacute setting

Background and purpose: Although reports of single cases of painful ophthalmoplegia (PO) are common, studies considering larger case series are lacking. Here, we aimed to determine the relative frequencies of ocular neuropathies, the causes, the usefulness of diagnostic procedures and the role of steroid treatment in PO. Methods: Between January 2006 and September 2012, 149 patients' charts who presented with diplopia in our emergency department were studied retrospectively. 34 of them met the inclusion criteria that included recent (≤3 days) symptom onset and a minimum of diagnostic work. Results: 32% of single or combined ocular motor nerve palsies were of diabetic microvascular etiology and most of themwere IIIrd or VIth nerve neuropathies. Themost useful, in terms of sensitivity and specificity of diagnostic test in the acute settingwas ESR,whereasMR-angiography and focused cavernous sinus imaging led to diagnosis in the post-acute phase. Pain response to steroids was non-specific, in contrast to palsy improvement after steroid administration which was indicative of Tolosa-Hunt syndrome or temporal arteritis. Conclusions: Although acute and subacute PO might be intuitively associated with Tolosa-Hunt syndrome or sinister pathology such as aneurysmal hemorrhage, our data show that these causes are far less common than diabetic microvascular palsies. Brain CT, MR-imaging of brainstem, cerebellum or hemispheres, CSF analysis and pain response to steroids are nonspecific and hence less helpful in order to arrive at a diagnosis. Instead, improved ocular motility after steroid treatment, as well as MR-angiography and cavernous sinus imaging appear more useful for this purpose. © 2013 Published by Elsevier B.V

Canal conversion after repositioning procedures: Comparison of Semont and Epley maneuver

Although the efficacy of Semont (SM) and Epley maneuvers (EM) for treatment of posterior canal benign paroxysmal positional vertigo (BPPV) is well established, data comparing SM and EM regarding maneuver-induced canal switch are lacking. We prospectively investigated 102 posterior canal BPPV patients after application of the Semont or the Epley maneuver and looked for the appearance of ipsilateral horizontal canal BPPV symptoms. Although treatment success was similar for SM and EM (67 and 76 %, respectively), there was a significant difference in posterior-to-horizontal canal switch rates. In particular, 4 of 51 patients (7.8 %) of the EM group converted to the geotropic type of horizontal canal BPPV, whereas none of the 51 SM patients exhibited a canal switch. All four patients were cleared with a single barbecue maneuver. Our data suggest a small but significant difference in canal switch rate between EM and SM, which could be partly explained by the higher number of maneuver steps during which the head is in the dependent position throughout the EM. © 2014 Springer-Verlag