ABSTRACT
Objective:To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM).Methods:A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP +) group, anti-HMGCR antibody positive (HMGCR +) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result:(1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP +, 8 (25.0%) with HMGCR +, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP +group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb ( P<0.01). The axial muscle score was lower than the distal limb score ( P<0.05).(3) Extramuscular manifestations of HMGCR + group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups ( P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP + group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR + group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion:IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP + group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR +group were more prone to myotonia potential and CRDs.
ABSTRACT
Axial myopathy is a general term for a group of myopathy involving the axial muscles. It refers to a group of skeletal myopathy in which paraspinal muscles are individually or significantly affected, with or without the involvement of whole body skeletal muscles. Axial muscle weakness is often ignored in clinical practice. The evaluation of axial muscle is mainly the evaluation of the paraspinal muscles (erector spinae) in current literature. The clinical manifestations of paraspinal muscle weakness are dropped head syndrome and camptocormia. Physical examination and skeletal muscle magnetic resonance imaging, especially the whole body muscle magnetic resonance scan, are vital for the evaluation of axial muscle. It is of great clinical significance to increase attention to the diagnosis and differentiation of axial myopathy, which is helpful to avoid missing treatable diseases and improve the understanding and early recognition of associated myopath.
ABSTRACT
Objective:To analyze the clinical manifestations, skeletal muscle pathology, electromyography, skeletal muscle magnetic resonance imaging and gene mutations of a family with distant-onset DnaJ (heat-shock protein 40) homolog subfamily B member 6 (DNAJB6) myopathy.Methods:A total of three generations with three cases of the disease in a family, inherited by autosomal dominant inheritance, were collected. The examination of muscle enzymes, left biceps biopsy, skeletal muscle magnetic resonance imaging (MRI) and electromyography, etc,were performed for the family 's proband. Whole-exon sequencing was performed to screen the proband for pathogenic genes, and Sanger sequencing technology was performed to verify mutation sites of the proband′s family members. Results:The proband is a 30-year-old male who began to show weakness in the distal muscles as a teenager, and then gradually developed to the proximal muscles, accompanied by muscle atrophy of the limbs, mainly affecting small muscles in the hands and distal muscles of the lower limbs. Muscle enzymes of the proband were slightly elevated. Skeletal muscle MRI indicated muscle atrophy and fatty degeneration in the proximal and distal extremities, which in the distal extremities were more severe, mainly affecting the muscle groups of the posterior group. Electromyography indicated chronic myopathic damage. Muscle pathology suggested chronic muscle fiber damage and rimmed vacuoles could be found. The proband was found a heterozygous mutation [c.298T>G(p.F100V)] in DNAJB6 gene by all-exon sequencing. Sanger sequencing confirmed that his brother (similar medical history) and the second daughter also had the same mutation, and the eldest daughter was not detected the mutation at the above site. The second daughter is not ill and is a carrier of the mutation. The father of the proband died of pancreatic cancer and had similar symptoms during his lifetime.Conclusions:The above mutation of DNAJB6 gene is the pathogenic gene of this family. The clinical features are adolescence-onset muscle weakness and atrophy in distal extremities. This is the first family report of distal-onset DNAJB6 myopathy caused by mutations at this site in China.