Myastenia-Inflammatory Myopathy (MG-IM) association has been described in less than 50 cases, as isolated reports or in few case series. In most cases, MG and IM onset occur simultaneously even if ...the overlapping clinical manifestations could lead to delay the diagnosis in the early stage of disease. In these cases, thymic pathology is present in more than 50% of cases. Pathological findings can be consistent of polymyositis (63%), dermatomyositis (25%) or granulomatosis (12%). Accurate clinical manifestations and severity of IM in MG, including muscle specific antibodies (MSA) and muscle MRI, have not been systematically investigated and focal or mild subclinical myositis have not been reported.
We observed that focal myositis or asymptomatic CK elevation can also occur in MG. In this review we have also retrospectively re-analyzed the clinical, serological, pathological and muscle imaging data from 13 patients with MG- IM from our cohort of 441 MG patients (2,9%). Clinical onset occurred simultaneously in 10/13 patients, whereas in 2 patients the IM appeared later in MG disease course (range 10–14 years) and conversely in 1 patient MG symptoms occurred later in IM disease course (4 years). Median age at disease onset was 51 year (range 24–73 years) regardless of clinical onset (MG or IM). Median clinical follow-up was 88 months (range 31–237 months). IM was suspected by CK elevation in all patients (ranging 800–3000 UI/L at first detection) and non-fatigable muscle weakness unresponsive to acetylcholinesterase inhibitors. All the patients presented mild to moderate MG symptoms. Three main categories of muscle involvement, sometimes overlapping, were recognizable: distal, proximal and subclinical myositits, leading to three main clinical groups (A,B,C) and two overlapping subgroups (A/B and B/C). Thymus pathology was present in 10/13 patients. Anti-AChR was detected in al all patients associated with anti-Titin and -RyR1 in those patients with thymoma. No MSA, nor MAA antibodies were detected. Muscle biopsy confirmed IM in all patients. In conclusion we redefined the clinical spectrum of muscle involvement in MG-IM association, which represent a continuum among 3 main clinical groups: distal, proximal and subclinical muscle involvement. Minimal muscle involvement and focal myositis could be underestimated among myasthenic patients and early aggressive immunotherapy could be required in focal group.
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•Inflammatory myopathy occurs in less than 3% of myasthenic patients.•All myasthenia-myositis patients have AChR antibodies and most of them has thymoma.•Three main clinical groups of muscle involvement: distal, proximal and subclinical.•Distal and subclinical involvement could be underestimated.•Distal myositis has poor clinical outcome and could require early aggressive therapy.
Abstract Introduction Eculizumab, a complement active antibody, and efgartigimod, an Fc fragment that blocks neonatal Fc receptor, are both approved to treat generalized myasthenia gravis (gMG) ...patients. The objective of this study is to describe the clinical response to both treatments in a real-life setting. Methods We collected baseline and follow-up clinical data using the Myasthenia Gravis-Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG). We included 63 patients, 32 treated with eculizumab and 31 with efgartigimod. Of the efgartigimod-treated patients, 22 were anti-acetylcholine receptor antibody-positive (AChR-Ab +) and 9 were AChR-Ab- (3 MuSK-Ab + and 6 seronegative). Results Both treatments showed similar efficacy relative to the MG-ADL scale reduction ( p = 0.237). Efgartigimod had a similar effect on both AChR-Ab + and AChR-Ab- ( p = 0.280). Eculizumab was superior to efgartigimod relative to the QMG score reduction for the entire dataset ( p = 0.003) and was more likely to achieve a clinical response at the QMG compared to efgartigimod (OR 1.373; p = 0.016). Steroid-sparing effect was higher for eculizumab than efgartigimod ( – 16.7 vs – 5.2 mg of the baseline daily dose at follow-up; p = 0.001). Mean speed of prednisone reduction was – 13.1 mg of the daily dose for each month of follow-up for eculizumab-treated patients and – 3.2 for efgartigimod ( p = 0.001). We found three serious events, all not related to treatment in the investigator’s opinion. One eculizumab-treated patient experienced a severe pneumonia and died despite treatment. Conclusions Our study provides evidence that eculizumab and efgartigimod can be used in clinical practice to reduce disability in gMG patients. Eculizumab-treated patients had a higher QMG response and steroid sparing effect. Efgartigimod may offer a more flexible schedule due to its cyclical use, no need for vaccination, and efficacy in AChR-Ab- patients.
Abstract Introduction Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease characterized by myotonia and progressive muscular weakness and atrophy. The aim of this study was to ...investigate the usefulness of longitudinal muscle MRI in detecting disease activity and progression in DM1, and to better characterize muscle edema, fat replacement and atrophy overtime. Materials and methods This is a prospective, observational, longitudinal study including 25 DM1 patients that performed at least two muscle MRIs. Demographic and genetic characteristics were recorded. Muscular Impairment Rating Scale (MIRS) and MRC score were performed within 3 months from MRIs at baseline (BL) and at follow-up (FU). We analysed 32 muscles of lower body (LB) and 17 muscles of upper body (UB) by T1 and STIR sequences. T1-, STIR- and atrophy scores and their variations were evaluated. Correlations between MRIs’ scores and demographic, clinical and genetic characteristics were analysed. Results Eighty (80%) of patients showed fat replacement progression at FU. The median T1 score progression (ΔT1-score) was 1.3% per year in LB and 0.5% per year in UB. The rate of fat replacement progression was not homogenous, stratifying patients from non-progressors to fast progressors (> 3% ΔT1-score per year). Half of the STIR-positive muscles at BL showed T1-score progression at FU. Two patients with normal MRI at baseline only showed STIR-positive muscle at FU, marking the disease activity onset. STIR positivity at baseline correlated with fat replacement progression (ΔT1-score; p < 0.0001) and clinical worsening at FU (ΔMRC-score; p < 0.0001). Sixty-five (65%) of patients showed STIR- and fat replacement-independent muscle atrophy progression, more evident in UB. Conclusions Muscle MRI represents a sensitive biomarker of disease activity, severity, and progression in DM1. STIR alterations precede fat replacement and identify patients with a higher risk of disease progression, while T1-sequences reveal atrophy and fat replacement progression before clinical worsening.
Objectives
Immune-mediated necrotizing myopathy (IMNM) is the most severe idiopathic inflammatory myopathy (IIM) and early aggressive poly-immunotherapy is often required to reduce long-term ...disability. The aim of this study is to investigate muscle MRI in IMNM as outcome measure for disease activity, severity, progression, response to treatment, and to better characterize the pattern of muscle involvement.
Methods
This is a retrospective, observational, cross-sectional, and longitudinal study including 22 IMNM patients, divided into three groups based on timing of first MRI and if performed before or under treatment. T1 score and percentage of STIR positive muscles (STIR%) were considered and analyzed also in relation to demographic, clinical and laboratory characteristics.
Results
STIR% was higher in untreated patients and in those who performed MRI earlier (
p
= 0.001). Pelvic girdle and thighs were in general more affected than legs. T1 score was higher in patients with MRI performed later in disease course (
p
= 0.004) with a prevalent involvement of the lumbar paraspinal muscles,
gluteus medius
and
minimus
,
adductor magnus
and hamstrings. 22% of STIR positive muscles showed fat replacement progression at second MRI. Higher STIR% at baseline correlated with higher risk of fat replacement at follow-up (
p
= 0.003); higher T1 score correlated with clinical disability at follow-up, with late treatment start and delayed treatment with IVIG (
p
= 0.03).
Interpretation
Muscle MRI is a sensitive biomarker for monitoring disease activity and therapy response, especially when performed early in disease course and before treatment start, and could represent a supportive outcome measure and early prognostic index in IMNM.
Objective
To test the complement inhibitor eculizumab in the treatment of MG exacerbation during therapy with the immune-checkpoint inhibitor (ICI) pembrolizumab, avoiding its discontinuation, which ...could be detrimental to oncologic course.
Methods
A 76-year-old male with non-thymomatous generalized anti-AchR + MG (MGFA class IVB), during treatment with pembrolizumab for colorectal cancer, developed a severe myasthenic exacerbation, refractory to steroids and IvIg. Eculizumab was started, without pembrolizumab discontinuation. The patient was prospectively followed using MGFA, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), MG Composite (MGC), and MG Quality of Life 15 (MG-QOL-15).
Results
After an 18-week follow-up, the patient presented a progressive improvement in scores on all scales, achieving a MGFA class IIIB. The percentage improvement was 40% in MG-ADL, 36% in MG Composite, and about 30% in QMG. Bulbar symptoms improved by about 70% in MG-ADL and MG Composite and 40% in QMG. Eculizumab was well tolerated and pembrolizumab regularly continued, with a good control of cancer progression.
Discussion
Eculizumab potentially offers a mechanism-based treatment of MG in patients under anti-programmed cell death protein 1 (PD-1) agents, without interfering with their mechanism of action and avoiding their discontinuation. Larger case series deserve to be evaluated.
Introduction
Mitochondrial alterations are a common finding in muscle biopsy of sporadic inclusion body myositis (s-IBM) and polymyositis with mitochondrial pathology (PM-Mito). Both disorders ...generally have poor treatment response. Nevertheless, mitochondrial myopathology has been rarely reported in dermatomyositis (DM) outside areas of perifascicular atrophy and a relationship with therapeutic outcome is not established.
Methods
We report on clinical, immunological, radiological, and myopathological findings of a case of severe, treatment-refractory anti-Mi-2-positive DM.
Results
A 77-year-old woman developed anti-Mi-2 DM with severe diffuse muscle weakness associated with abundant mitochondrial abnormalities at muscle biopsy, beside the typical features of inflammatory myopathy. The patient was poorly responsive to multiple-line therapies and finally anti-JAK (anti-Janus activated kinase) was administered, leading to partial clinical improvement.
Discussion
Given the usual satisfactory treatment response and favorable outcome of anti-Mi-2 DM, we suppose that mitochondrial dysfunction on muscle biopsy could represent a marker of disease severity in DM, predicting a worse response to treatment and a poor clinical outcome. JAK-inhibitors could represent a good treatment option in refractory anti-Mi-2 DM with mitochondrial abnormalities.
Background and purpose
Cardiac involvement is observed in about 80% of subjects with myotonic dystrophy type 1 (DM1) and is mainly characterized by cardiac conduction and/or rhythm abnormalities ...(CCRAs), possibly leading to sudden cardiac death (SCD). Our objective was to investigate whether the gender difference may influence the cardiac involvement and SCD in DM1.
Methods
We analyzed prevalence and incidence of cardiological abnormalities in males versus females in 151 consecutive DM1 patients over a 35‐year follow‐up period.
Results
Fifty‐five patients, 35 males (62.5%) and 20 females (42.5%), developed some type of CCRA during the follow‐up period (mean 7.82 ± 6.21 years). CCRA overall, and specifically cardiac conduction abnormalities (CCAs), were significantly more frequent in males than in females (p = 0.043 and p = 0.031, respectively). CCRAs progressed in 16 males (45.7%) and six females (30%). Twenty‐four patients, 14 males (25.0%) and 10 females (21.3%), died during the follow‐up. Nine of them, six males (10.7%) and three females (6.4%), had SCD. After correction for Muscular Impairment Rating Scale progression, cytosine thymine‐guanine expansion, and follow‐up duration, a higher prevalence of CCAs was independently associated with male gender (p = 0.039), but independent association with gender was not detected for CCRAs overall, cardiac rhythm abnormalities, and SCD prevalence, even if prevalence was higher in males than females.
Conclusions
The overall risk of occurrence of CCAs in DM1 is significantly higher in males than females regardless of genetic background and disease severity and progression. Moreover, the data also suggest a similar impact for male gender for CCRAs overall, CCAs, and SCD even if not statistically significant.
The overall risk of cardiac abnormalities in myotonic dystrophy type 1 is significantly higher in males regardless of genetic background and disease severity and progression.
Introduction
Myasthenia gravis-inflammatory myopathy (MG-IM) association has been rarely reported as specific clinical entity characterized by variable myositis manifestations, ranging from ...subclinical to diffuse muscle involvement with characteristic distal upper limb weakness. Although, in view of this, it has been hypothesized that distal muscle weakness in MG-IM could be due to the muscle inflammation instead of a pure neuromuscular transmission impairment, a biopsy-proven myositis process of distal muscles of upper limbs has not yet been provided.
Methods
We report on clinical, immunological, and myopathological characterization of a novel case affected by MG-IM association showing the typical distal upper limb weakness, including muscle biopsy of a weak forearm muscle.
Results
Histological and immunohistochemical studies showed a marked inflammatory process on muscle biopsy of
extensor digitorum communis.
The patient, a 47-year-old man with 10-year history of anti-acetylcholine receptor (AChR) and anti-titin antibody-positive MG with thymoma, developed a progressive, diffuse, and non-fatigable weakness predominant in distal upper limb muscles, unresponsive to acetylcholinesterase inhibitors associated to myalgia and creatine kinase (CK) elevation.
Discussion
We provide the histopathological evidence of a prominent inflammatory process responsible of distal upper limb weakness in MG-IM association. Muscle biopsy does not reveal any typical histopathological feature of other nosologically definite inflammatory myopathy, leading MG-IM association to come close to the group of overlap-myositis (OM) with the myopathological features of non-specific myositis (NSM).
Introduction
Muscle ultrasound is a fast, non-invasive and cost-effective examination that can identify structural muscular changes by assessing muscle thickness and echointensity (EI) with a ...quantitative analysis (QMUS). To assess applicability and repeatability of QMUS, we evaluated patients with genetically confirmed facioscapulohumeral muscular dystrophy type 1 (FSHD1), comparing their muscle ultrasound characteristics with healthy controls and with those detected by MRI. We also evaluated relationships between QMUS and demographic and clinical characteristics.
Materials and methods
Thirteen patients were included in the study. Clinical assessment included MRC sum score, FSHD score and The Comprehensive Clinical Evaluation Form (CCEF). QMUS was performed with a linear transducer scanning bilaterally
pectoralis major
,
deltoid
,
rectus femoris
,
tibialis anterior
and
semimembranosus muscles
in patients and healthy subjects. For each muscle, we acquired three images, which were analysed calculating muscle EI by computer-assisted grey-scale analysis. QMUS analysis was compared with semiquantitative 1.5 T muscle MRI scale.
Results
All muscles in FSHD patients showed a significant increased echogenicity compared to the homologous muscles in healthy subjects. Older subjects and patients with higher FSHD score presented increased muscle EI.
Tibialis anterior
MRC showed a significant inverse correlation with EI. Higher median EI was found in muscles with more severe MRI fat replacement.
Conclusions
QMUS allows quantitative evaluation of muscle echogenicity, displaying a tight correlation with muscular alterations, clinical and MRI data. Although a confirmation on larger sample is needed, our research suggests a possible future application of QMUS in diagnosis and management of muscular disorders.
