Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb？girdle Muscle

Background： Congenital myasthenic syndromes （CMSs） are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation （c.5302G〉C） of AGRN in a Chinese CMS pedigree. Methods： We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy （including 17 CMS genes）. Results： In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband＇s two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation （c.5302G〉C, p.A1768P） of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions： This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.

A study on post-exercise facilitation in 11 patients with Lambert-Eaton myasthenic syndrome

Objective To study the operation method of the post-exercise facilitation(PEF)in Lambert-Eaton myasthenic syndrome(LEMS),and to seek for the meaning of PEF in clinical work.Methods Eleven patients with LEMS were included to accept the PEF and the repetitive nerve stimulation(RNS)test.When performing the PEF test,compound muscle action potentials(CMAPs)of abductor digitiminimi were recorded after a specified time

Voltage gated calcium channel antibody-related neurological diseases

Voltage gated calcium channel(VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as nonparaneoplastic cerebellar degeneration. Most patients with VGCC-antibody-positivity have small cell lung cancer(SCLC). Lambert-Eaton myasthenic syndrome(LEMS)is an autoimmune disease of the presynaptic part of the neuromuscular junction. Its classical clinical triadis proximal muscle weakness, areflexia and autonomic dysfunction. Fifty to sixty percent of LEMS patients have a neoplasia, usually SCLC. The co-occurrence of SCLC and LEMS causes more severe and progressive disease and shorter survival than non-paraneoplastic LEMS. Treatment includes 3,4 diaminopyridine for symptomatic purposes and immunotherapy with prednisolone, azathioprine or intravenous immunoglobulin in patients unresponsive to 3,4 diaminopyridine. Paraneoplastic cerebellar degeneration(PCD) is a syndrome characterized with severe, subacute pancerebellar dysfunction. Serum is positive for VGCC antibody in 41%-44% of patients, usually with the co-occurrence of SCLC. Clinical and electrophysiological features of LEMS are also present in 20%-40% of these patients. Unfortunately, PCD symptoms do not improve with immunotherapy. The role of VGCC antibody in the immunopathogenesis of LEMS is well known whereas its role in PCD is still unclear. All patients presenting with LEMS or PCD must be investigated for SCLC.