Edrophonium Chloride

In recent years, immune checkpoint inhibitors (ICI) have become the standard treatments for various cancers. These drugs are monoclonal antibodies targeting mols. such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and PD-1 ligand (PD-L1). ICI activate the immune system to eliminate malignancies.Here, we report a case of myositis/myocarditis with multiple myositis-specific-antibodies (MSAs) and myositis-associated-antibodies (MAAs) during use of pembrolizumab, a PD-1 inhibitor, which improved with immunotherapy.The result of ice pack test was neg. in this case. I.v. administration of edrophonium did not improve ptosis (1-A), grip strength and upper/ lower limb muscle strength. As described above, the various tests to detect myasthenic symptoms were neg.When clinicians encounter neuroimmune disorders during ICI treatment, it is sometimes difficult to determine whether they are drugderived reactions or tumor-associated symptoms.If the symptoms are drug-derived, the ICI should be discontinued, however, if the symptoms are tumor-related, the ICI should be continued. Simultaneous-positivemultiple MSAs is suggestive of an ICI-derived autoimmune response and may be a useful insight for clinicians treating myositis during ICI use to select a more appropriate treatment.

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous neuromuscular disorder characterized by muscle weakness and caused by mutations in more than 35 different genes. This condition should not be overlooked as a subset of patients with CMS are treatable. However, the diagnosis of CMS is often difficult due to the broad variability in disease severity and course.

A five-year-old boy without remarkable family history was born with marked general muscle hypotonia and weakness, respiratory insufficiency, anomalies, and multiple joint contractures. Congenital myopathy was suspected based upon type 1 fiber predominance on muscle biopsy. However, he was diagnosed with CMS at age 4 years when his ptosis and ophthalmoplegia were found to be improved by edrophonium chloride and repetitive nerve stimulation showed attenuation of compound muscle action potentials. An exome sequencing identified a compound heterozygous missense variant of c.737C > T (p.A246V) and a novel intronic insertion c.1166 + 4_1166 + 5insAAGCCCACCAC in RAPSN. RT-PCR analysis which showed the skipping of exon 7 in a skeletal muscle sample confirmed that the intronic insertion was pathogenic. His myasthenic symptoms were remarkably improved by pyridostigmine.

The patient's diagnosis of CMS was confirmed by exome sequencing, and RT-PCR revealed that the skipping of exon 7 in RAPSN was caused by a novel intronic insertion. The genetic information uncovered in this case should therefore be added to the collection of tools for diagnosing and treating CMS.