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Background Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. Methods We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C > T, MTR c.2756A > G, MTRR c.66A > G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR + MG patients. A total of 526 AChR + MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. Results The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia ( P = 0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)]. Conclusions The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR + MG patients. [ABSTRACT FROM AUTHOR]

Introduction Myasthenia gravis (MG) with autoantibodies to muscle-specific tyrosine kinase (MuSK) represents a distinct type of disease, as compared MG with antibodies against acetylcholine receptor (AchR-Abs). MuSK-MG patients have peculiar clinical features characterized by predominant oculo-bulbar symptoms and a lack of response to conventional MG treatments. Since the role of electrophysiological tests in MuSK patients is still argued, our aim was to investigate their electrophysiological profile in order to arise a light over this darkness. Methods We retrospectively evaluated repetitive nerve stimulation (RNS) and single-fibre electromyography (SF-EMG) reports of 63 MuSK patients, at the time of MG diagnosis, and we compared them with 35 non-timomatous AChR-Abs positive patients matched with MuSK group according to gender, age at onset of MG, age at MG diagnosis and severity of the disease. Disease severity was graded according to Myasthenia Gravis Foundation of America (MGFA) classification. Seronegative patients and thymoma-associated MG patients were excluded from the study. Results Sixty-three MuSK patients (11 males; 52 females; mean age at MG onset: 37 ± 2.0; mean age at diagnosis: 38.7 ± 2.0) and 35 AChR-Abs positive patients (9 males; 26 females; mean age at MG onset: 31.2 ± 2.7: mean age at diagnosis: 33.1 ± 2.5) were enrolled in the study. Fifty-nine MuSK patients (93.6%) and 31 AChR-Abs positive patients (88.5%) underwent RNS, whereas SF-EMG was tested in 17 MuSK patients and in 7 AChR-Abs patients. RNS showed a significant decrement in a higher percentage of AChR-Abs positive patients than the MuSK group (p < 0.0008) whereas no significant difference was found in the two groups regarding SF-EMG (p = 0.5). RNS was positive in 30 MuSK patients (50.8%), negative in 25 MuSK patients (42.4%) and in 4 patients only facial muscles examined showed a significant decrement whereas the examination of extremity muscles was negative. On the other hand, RNS was positive in 27 AChR-Abs positive patients (87%), it was negative in three patients (9.7%) and in one patient only one examined muscle showed a significant decrement. In MuSK positive group, proximal muscles showed a significant decrement, more than distal ones (p < 0.02) whereas no significant differences were found in controls. In MuSK patients, the presence of pathological RNS was not in correlation neither with MG severity (p = 0.9) nor with the length of drug-free-period (p = 0.4). Increased jitter was present in 14 (82.3%) MuSK and 5 (71.4%) AChR-Abs patients; it was absent in 2 MuSK patients (11.7%) and in 2 AChR-Abs positive patients (28.5%). In one MuSK patient SF-EMG was borderline. Conclusion While SR-EMG positivity was significantly higher in AChR-Abs group, there was no difference regarding SF-EMG. In MusK group, the decrement of RNS was more evident in proximal muscles while RNS in distal muscles can be negative. Although neurophysiological evaluation is still important for MG diagnosis, it plays a secondary role after anti-MuSK titration. [ABSTRACT FROM AUTHOR]