Bloc atrio-ventriculaire de grade III compliquant une myocardite au décours d’un traitement par anti-PD1 : observation d’un cas et revue de la littérature

IntroductionImmune Checkpoint Inhibitor (ICI) therapy is now a standard of care in numerous cancers with very promising results. Nevertheless, adverse events, and especially immune-related adverse events (irAEs) not reported during clinical trials, are emerging and can be life-threatening.ObservationWe report here a teachable case of a 80 year-old man, of third-degree atrioventricular block consecutive to myocarditis associated with the administration of nivolumab (anti-PD1) monotherapy.ConclusionMyocarditis occurring during ICI treatment is a rare but potentially lethal event. Daily serum troponin level seems to predict ICI-related myocarditis but interpretation could be difficult in the context of associated myositis. Echocardiography and cardiac MRI are also useful but can remain negative. Electrocardiogram is a cornerstone of myocarditis diagnosis. In case of cardiac involvement, continuous heart rhythm monitoring should be performed in addition to the administration of high-dose corticosteroids therapy and the cessation of ICI therapy. Add-on treatments should be discussed with a well-trained multidisciplinary team.     

Colchicine Treatment in Children With Familial Mediterranean Fever: Is it a Risk Factor for Neuromyopathy?

BackgroundWe cared for a 17-year-old adolescent with familial Mediterranean fever under colchicine treatment. Because of the increased creatinine kinase level (3937 U/L) observed in this individual, we planned to assess all pediatric patients with familial Mediterranean fever under colchicine treatment to detect any resultant neuromyopathy.MethodsThe study included 88 children with familial Mediterranean fever who were receiving colchicine. The patient with myopathy was not included in the study. Serum creatinine kinase levels were measured and nerve conduction studies were carried out in all patients.ResultsThe study included 88 patients (47 female, 53.4%) with an average age of 10.1 ± 3.35 years. The average period of colchicine use was 28.25 ± 17.66 months. Side effects of colchicine were detected in 10 patients (11%)—as diarrhea in eight patients, leukopenia in one patient, and hair loss in one patient. Nerve conduction studies determined incidental carpal tunnel syndrome in only one patient.ConclusionsOur study did not suggest an elevated risk of neuromyopathy associated with the use of colchicine for familial Mediterranean fever.     

Novel TPM3 mutation in a family with cap myopathy and review of the literature

Cap myopathy is a rare congenital myopathy characterized by the presence of caps within muscle fibres and caused by mutations in ACTA1, TPM2 or TPM3. Thus far, only three cases with TPM3-related cap myopathy have been described. Here, we report on the first autosomal dominant family with cap myopathy in three-generations, caused by a novel heterozygous mutation in the alpha-tropomyosin-slow-encoding gene (TPM3; exon 4; c.445C>A; p.Leu149Ile). The three patients experienced first symptoms of muscle weakness in childhood and followed a slowly progressive course. They presented generalized hypotrophy and mild muscle weakness, elongated face, high arched palate, micrognathia, scoliosis and respiratory involvement. Intrafamilial variability of skeletal deformities, respiratory involvement and mild cardiac abnormalities was noted. Muscle MRI revealed a recognizable pattern of fatty muscle infiltration and masseter muscle hypertrophy. Subsarcolemmal caps were present in 6–10% of the fibres and immunoreactive with anti-tropomyosin antibodies. We conclude that the MRI-pattern of muscle involvement and the presence of masseter muscle hypertrophy in cap myopathy may guide molecular genetic diagnosis towards a mutation in TPM3. Regular respiratory examinations are important, even if patients have no anamnestic clues. We compare our findings to all cases of cap myopathy with identified mutations (n = 11), thus far reported in the literature.     

Nonvolitional assessment of muscle endurance in idiopathic inflammatory myopathies: There is no relationship between patient‐reported fatigue and muscle fatigability

Introduction: We investigated whether muscle endurance differs between IIM patients and controls and if a relationship exists between perceived fatigue and poor muscle endurance. Methods: Quadriceps contractility, measured using femoral nerve stimulation (TwQ), and strength, measured using maximal voluntary contraction (MVCQ), were assessed in 20 IIM patients and matched controls. Quadriceps endurance was assessed using repetitive electrical stimulation (3 minutes). Time for force to fall to 70% initial force was determined (T70). Reported fatigue was measured using the FACIT‐F/Fatigue Severity Scales. Results: TwQ and MVCQ were lower and perceived fatigue greater for patients. There was no difference in T70 between groups. No relationships were observed between perceived fatigue and endurance (T70). Conclusions: IIM patients reported more fatigue and were weaker than controls, but there was no difference in muscle endurance. Endurance and strength were unrelated to reported fatigue measures. Mechanisms driving perceived IIM fatigue are likely to be multifactorial. Muscle Nerve 50 : 401–406, 2014     

No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis,frontotemporal dementia,and inclusion body myopathy

Inclusion body myopathy (IBM) associated with Paget disease of the bone, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), sometimes called IBMPFD/ALS or multi system proteinopathy, is a rare, autosomal dominant disorder characterized by progressive degeneration of muscle, brain, motor neurons, and bone with prominent TDP-43 pathology. Recently, 2 novel genes for multi system proteinopathy were discovered; heterogenous nuclear ribonucleoprotein (hnRNP) A1 and A2B1. Subsequently, a mutation in hnRNPA1 was also identified in a pedigree with autosomal dominant familial ALS. The genetic evidence for ALS and other neurodegenerative diseases is still insufficient. We therefore sequenced the prion-like domain of these genes in 135 familial ALS, 1084 sporadic ALS, 68 familial FTD, 74 sporadic FTD, and 31 sporadic IBM patients in a Dutch population. We did not identify any mutations in these genes in our cohorts. Mutations in hnRNPA1 and hnRNPA2B1 prove to be a rare cause of ALS, FTD, and IBM in the Netherlands.     

“Give me strength” – inflammatory muscle disease in children

Juvenile dermatomyositis is the most common idiopathic inflammatory myopathy of childhood. Management focuses on early aggressive suppression of inflammation to induce sustained remission and prevent complications such as muscle contractures or calcinosis. Advances in diagnostic modalities and treatment have led to improved mortality and morbidity, but long-term risks remain significant. Early disease recognition with appropriate referral and management by a specialist multidisciplinary team is crucial. This review focuses on juvenile dermatomyositis including differential diagnosis from other conditions causing muscle weakness in children.     

A new method for isolation of cardiac myocytes by percutaneous endomyocardial biopsy

The objective of this study was to demonstrate the feasibility of isolating viable canine cardiac myocytes from percutaneous right ventricular endomyocardial biopsy specimens. Although histologic data can be obtained from percutaneous endomyocardial biopsies, this approach has not been used as a source of viable cells for evaluating pathological conditions. Study of isolated viable myocytes may provide insight into the electrical, biochemical, and physiologic functions of the heart. Using a standard 8F sheath, a 5F bioptome was introduced via the right femoral vein and advanced to the right ventricle, where 85 biopsies were obtained from 8 mongrel dogs. An average of six biopsy specimens were pooled for processing to provide adequate tissue substrate. This resulted in 14 groups of specimens which were then processed to isolate individual myocytes. Viable myocytes were striated, rod-shaped, and excluded trypan blue dye. Nonviable myocytes were rounded, had no cross-striations, and did stain with trypan blue. Partially-injured myocytes contracted spontaneously and had a region of loss of cross-striations. The average number of viable cells recovered per group of pooled specimens was 1.8 × 10⁴ (1.8 × 10³ cells/mg of tissue). The greatest yield of viable myocytes recovered was 8.0 × 10⁴, which represented a viability of 90% by trypan blue dye exclusion and morphological criteria. Percutaneous right ventricular endomyocardial biopsy is a novel method for obtaining viable cardiac myocytes. Its feasibility and utility in humans warrant further investigation. © 1996 Wiley-Liss, Inc.     

Muscle-nerve involvement in autosomal dominant progressive external ophthalmoplegia with hypogonadism

Sixteen members of a family with a history of autosomal dominant progressive external ophthalmoplegia (adPEO) with hypogonadism were examined. The muscular involvement commenced cranially and descended in relation to increasing disease duration. The neuromuscular signs were PEO, dysarthria, dysphonia, limb muscle weakness with wasting, absence of Achilles tendon reflexes, and distal vibration sensory loss. The electromyogram (EMG) was myopathic in facial and proximal limb muscles. Neurogenic involvement was suspected in a few tibial anterior muscles. Neurography showed signs of axonal neuropathy correlated to clinical signs. F-responses were reduced in number or absent in peroneal nerves, and did not correlate to clinical signs or disease duration. Muscle biopsies in advanced cases had structural abnormalities of mitochondria, ragged-red fibers, and focal cytochrome c oxidase deficiency. A combination of muscle-nerve involvement with PEO, Achilles tendon areflexia, distal vibration sensory impairment, myopathic EMG, and abnormally low sural nerve responses seems to be typical of this type of mitochondrial disorder. © 1996 John Wiley & Sons, Inc.     

Computerized tomography and magnetic resonance muscle imaging in Miyoshi's myopathy

We describe clinical, pathological, and muscle imaging findings in a patient with an early adult-onset progressive muscular weakness in association with atrophy beginning in the legs and involving both gastrocnemi in particular. Muscle biopsy findings showed a severe dystrophic process with no vacuoles, consistent with Miyoshi's myopathy. Computerized tomography and magnetic resonance imaging scans were used to provide an ongoing permanent record of the various stages of the disease. © 1996 John Wiley & Sons, Inc.