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Corrado Angelini,1 Sara Martignago,2 Michela Bisciglia21IRCCS S Camillo, Via Alberoni, Venice, Italy; 2Department of Neurosciences, University of Padova, Via Giustiniani 5, 35128, Padova, ItalyAbstract: Autoimmune myasthenia gravis (MG) is a neuromuscular disorder caused by autoantibodies directed against the acetylcholine receptor (AChR). Current symptomatic therapy is based on acetylcholinesterase (AChE) drugs. The available long-term current therapy includes steroids and other immunomodulatory agents. MG is associated with the production of a soluble, rare isoform of AChE, also referred as the “read-through” transcript (AChE-R). Monarsen (EN101) is a synthetic antisense compound directed against the AChE gene. Monarsen was administered in 16 patients with MG and 14 patients achieved a clinically significant response. The drug is now in a Phase II study. Further investigations are required to confirm its long-term effects.Keywords: myasthenia gravis, antisense oligonucleotides, acetyl cholinesterase, EN101

Dominant mutations in CACNA1S gene mainly causes hypokalemic periodic paralysis (PP)(hypoPP). A 68-year-old male proband developed a progressive proximal weakness from the age of 35. Muscle biopsy showed atrophic fibers with vacuoles containing tubular aggregates. Exome sequencing revealed a heterozygous p.R528H (c.1583G>A) mutation in the CACNA1S gene. CACNA1S-related HypoPP evolving to persistent myopathy in late adulthood is a well-known clinical condition. However, isolated progressive myopathy (without PP) was only exceptionally reported and never with an early onset. Reporting a case of early onset CACNA1S-related myopathy in a patient with no HypoPP we intend to alert clinicians to consider it in the differential diagnosis of younger adult-onset myopathies especially when featuring vacuolar changes.

Muscle phosphorylase kinase b deficiency (PhK) is a rare disorder of glycogen metabolism characterized by exercise-induced myalgia and cramps, myoglobinuria and progressive muscle weakness. PhK deficiency is due to mutations in the PHKA1 gene inherited in an X-linked manner and is associated to glycogenosis type VIII (GSD VIII also called GSD IXd). PHKA1 gene codes for the αM subunit of the PhK, a multimeric protein complex responsible for the control of glycogen breakdown in muscle. Until now, few patients have been reported with X-linked recessive muscle PhK deficiency due to PHKA1 mutations. All reported patients presented with exercise intolerance and mild myopathy and one of them had cognitive impairment, leading to speculate about a central nervous system involvement in GSD VIII. Here we report in a sibling a novel mutation in the PHKA1 gene associated with a progressive myopathy, exercise intolerance, muscle hypertrophy and cognitive impairment as an associated feature. This report expands the genetic and clinical spectrum of the extremely rare PHKA1-related PhK deficiency and presents new evidences about its involvement in brain development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Movement disorders following heart surgery are very unusual. Post-pump chorea is mainly a pediatric complication of heart surgery, typically manifesting after a latent period of normality and is usually related with long extracorporeal circulation time and deep hypothermia. We report a 73-year-old woman, without risk factors predisposing to paroxysmal movement disorders, presenting acute choreoathetoid movements 5 days after aortic valvular replacement with normal extracorporeal circulation time and perioperative normothermia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We studied 15 patients suffering from nephrotic syndrome (NS) in bioptically-accertained primary and secondary glomerulopathies responding poorly to the common pharmacological treatment. They were monitored for one year by assessing their immunological and kidney functionality parameters, especially proteinuria. The patients underwent 3 apheretic sittings using the cascade double-filtration technique. After the third apheretic sitting the patients received metilprednisolone 300 mg/m2. This therapy was repeated every month for 6 months. At the end of the apheretic cycle it was shown that all patients had responded well to the therapy with a dramatic decrease in proteinuria, maintenance and/or recuperation of kidney functionality and improvement of lipidic asset; these data remained unchanged over time. Considering our preliminary results, we believe that therapeutic apheresis has a precise function in refractory nephrotic syndrome and, in particular, we propose the use of the cascade double-filtration technique.

Systemic Lupus Erythematosus (SLE) is a pathology of unknown cause, characterized by tissue and cellular damage, secondary to production of autoantibodies and to deposition of immunocomplexes. Lupus nephritis is one of the most common complications of SLE. Our purpose is to propose a therapeutic protocol for patients suffering from Lupus nephritis. This consists of Plasmapheresis associated with pharmacological therapy so that dosage of immunosuppressors can be reduced and consequently also the side effects of the pharmacological therapy.