<b><i>Objectives:</i></b> A number of worldwide studies have highlighted a rising incidence of myasthenia gravis (MG) over the past few decades. This is largely due to an increase in numbers in older patients. To establish whether this was a consistent finding in the United Kingdom, we conducted a large, 4-year prospective cohort study of all known patients with new-onset MG in the East Midlands of the United Kingdom. <b><i>Methods:</i></b> Between 2014 and 2018, all 120 patients with a new diagnosis of MG who were residing in the East Midlands were enrolled. <b><i>Results:</i></b> Median age at disease onset was 63 years (78% aged over 50 years) and most patients (57%) were male. The average annual incidence rate (IR) was 17.6/1,000,000 (95% CI 10.7–28.6). IRs remained stable between 2014 and 2018 except for rising IRs in patients over 65 years of age (<i>p</i> value for trend, &#x3c;0.001). <b><i>Conclusions:</i></b> Twenty years after the last comprehensive prospective incidence survey of MG in the east of England, we have demonstrated a rising incidence. The greatest increases seen were in patients over 65 years. Given the rigorous study methods employed, future replicate prospective studies from the same region will establish whether these rising figures are due to biological factors, independent of improved case ascertainment.

Objective To determine a predictive factor for the risk of conversion from ocular myasthenia gravis ( OMG ) to generalized MG ( GMG ) in a prospective study. Methods RNA was isolated from serum samples and detection of micro RNA (mi RNA ) expression analyzed with qPCR . In the discovery set, 179 human mi RNA s were assayed for profiling of five OMG patients and four age‐ and gender‐matched healthy controls. Based on the specific accumulation pattern of 19 mi RNA s from the discovery set, in addition to mi RNA s previously found elevated in generalized MG ( GMG ; miR‐150‐5p and miR‐30e‐5p), 21 mi RNA s were subsequently analyzed in a validation cohort of 83 OMG patients (82 immunosuppression treatment naive; 49 male) within 3 months of diagnosis and at a follow‐up visit (median duration 28 months from first visit). Results Thirteen patients generalized 14.8 ± 12.0 months after the diagnosis and the majority (85%) belonged to the late onset MG group. Two mi RNA s were significantly higher in secondary GMG ( SGMG ) patients compared to OMG patients with late onset MG : miR‐30e‐5p (9.1 ± 0.5 vs. 6.3 ± 0.9; P < 0.0001) and miR‐150‐5p (7.4 ± 1.1 vs. 6.4 ± 1.1; P = 0.01). The sensitivity for miR‐30e‐5p in differentiating OMG and SGMG was 96% in all OMG patients and 100% in late onset OMG patients. Interpretation This is the first study to describe a potential predictive factor associated with the risk of generalization for patients with OMG . Raised levels (>8) of miR‐30e‐5p at initial presentation in patients with ocular MG symptoms, give a predictive cut‐off for subsequent generalization of 96–100%.

There are no biomarkers for late onset myasthenia gravis (LOMG; onset >50 years). We evaluated circulating microRNA in a discovery cohort of 4 LOMG patients and 4 healthy controls and in a prospective diagnostic validation cohort of 73 LOMG patients (48 male) with longitudinal follow-up samples. In immunosuppression naïve patients, levels of miRNAs miR-150-5p, miR-21-5p and miR-30e-5p decreased in parallel with clinical improvement after initiation of immunosuppression and their levels positively correlated with the clinical MG composite score. Levels of miR-150-5p and miR-21-5p were lower in patients with ocular compared to generalized LOMG. Circulating miR-150-5p, miR-21-5p and miR-30e-5p correlate with the clinical course in LOMG.