Shear wave elastography combined with electromyography to assess the effect of botulinum toxin on spastic dystonia following stroke : A pilot study

Shear wave elastography (SWE) is a method for carrying out a quantitative assessment of the mechanical properties of soft tissues in terms of stiffness. In stroke survivors, the paretic muscles may develop hypertonia due to both neural-mediated mechanisms and structural alterations with consequent muscular fibrous-fatty remodeling. Fourteen adult patients with spastic dystonia following stroke were recruited. Muscle hypertonia was assessed using the modified Ashworth scale (MAS). Muscle activation was measured by surface electromyography (sEMG) with the selected muscle in shortened (spastic dystonia) and stretched (dynamic stretch reflex) positions. SWE was performed on a selected paretic muscle and on the contralateral non-paretic one to calculate shear wave velocities (SWV) along and across muscular fibers. The modified Heckmatt scale (MHS) pattern was also determined. All evaluations were performed shortly before BoNT-A injections (T0) and one month later (T1). All SWV on paretic muscles were higher than contralateral non-paretic ones (p < 0.01). After BoNT-A injection, a significant reduction in MAS (p = 0.0018), spastic dystonia (p = 0.0043), and longitudinal SWE measurements, both in shortened (p = 0.001) and in stretched muscular conditions (p = 0.0029), was observed. No significant changes in SWV on non-paretic muscles were observed. Higher SWV resulted along the direction of muscular fibers vs. across them (p = 0.001). No changes resulted from the MHS evaluations after BoNT-A. There was a positive correlation between MHS scores and SWV values while the muscle was in the shortened position, but not with spastic dystonia recorded by sEMG. This is the first study evaluating the effect of BoNT-A on muscle hypertonia following stroke, assessed by both SWE and sEMG. These findings support SWE as a useful method to disclose intrinsic muscular remodeling, independently of the effect of spastic dystonia, in particular, while muscles were assessed in a neutral position. SWE measurements of muscle stiffness cannot tell apart neural-mediated and intrinsic muscle hypertonia. Interestingly, when sEMG activity is very limited, as in spastic muscles kept in a shortened position, SWE can provide a measurement of stiffness due almost completely to intrinsic muscle changes. Alongside sEMG, SWE could aid clinicians in the assessment of responses to treatments

Interferons reshape the 3D conformation and accessibility of macrophage chromatin

Engagement of macrophages in innate immune responses is directed by type I and type II interferons (IFN-I and IFN-γ, respectively). IFN triggers drastic changes in cellular transcriptomes, executed by JAK-STAT signal transduction and the transcriptional control of interferon-stimulated genes (ISG) by STAT transcription factors. Here, we study the immediate-early nuclear response to IFN-I and IFN-γ in murine macrophages. We show that the mechanism of gene control by both cytokines includes a rapid increase of DNA accessibility and rearrangement of the 3D chromatin contacts particularly between open chromatin of ISG loci. IFN-stimulated gene factor 3 (ISGF3), the major transcriptional regulator of ISG, controlled homeostatic and, most notably, induced-state DNA accessibility at a subset of ISG. Increases in DNA accessibility correlated with the appearance of activating histone marks at surrounding nucleosomes. Collectively our data emphasize changes in the three-dimensional nuclear space and epigenome as an important facet of transcriptional control by the IFN-induced JAK-STAT pathway