Value of magnetic resonance imaging for evaluating muscle inflammation: insights from a new mouse model of myositis

Abstract

Inflammatory myopathies or myositides represent a group of severe skeletal muscle diseases characterized by muscle weakness, elevation of serum creatine kinase levels and muscle inflammatory cell infiltrates. Despite the contribution of a growing number of myositis-specific autoantibodies and the existence of characteristic dermatological features in dermatomyositis, the definitive diagnosis of myositis requires pathological examination of a muscle biopsy [1, 2]. To limit false negatives, this biopsy should be performed in an area of active disease [2]. In this context, magnetic resonance imaging (MRI) has gained interest since T1-weighted images are able to determine muscle damage such as atrophy, fatty infiltration and their distribution [3, 4] while T2-weighted images help to detect edema and thus may inform on the activity of the disease, i.e. muscle inflammatory infiltrates. This article is protected by copyright. All rights reserved.

Icos gene disruption in non‐obese diabetic mice elicits myositis associated with anti‐troponin T3 autoantibodies

“…The incidence of diabetes, body weight, myopathy clinical score [13] and front paw strength (grip test) of Icos −/− NOD mice were determined over time. Icos −/− NOD mice did not develop diabetes in contrast to Icos +/+ NOD mice (Figure 1A), but they showed signs of myopathy from 24 weeks of age, reaching a prevalence of 100% at 35 weeks, reflecting a slowly progressive disease (Figure 1B).…”

“…Locomotor activity was evaluated at 34 weeks of age using the Catwalk XT gait analysis system (Noldus). For the clinical score, spontaneous muscle disability was separately scored for the two front paws and for the two hind ones as described in [13]: 0, normal; 1, mild muscle weakness with a tendency for spontaneous flexion of paws but conserved walk on a grid; 2, moderately impaired walk on a grid; and 3, severe disability to walk on a grid (with intermediate 0.5 values when required). Then, a global score was computed by adding the latter two values to a global limb disability score during a brief tail suspension assay (from 0, normal to 3, hunched up with no spontaneous movement; interval 0.5), plus 1 supplemental point when breathing difficulties were apparent.…”

IFNγ causes mitochondrial dysfunction and oxidative stress in myositis

“…The degree of myopathy was quantified using a clinical score from 0 to 10 as previously described 66 . Briefly, this consisted in a cumulative score based on the sum of two separate scores (from 0 to 3) given to front and hind paws based on the degree of spontaneous limb flexion and impairment of march on a grid, a global score (from 0 to 3) based on hunch position when holding by tail suspension, and an additional point ( + 1) given for abnormal breathing.…”