Background Complement inhibitors are primarily used for symptomatic/refractory but stable myasthenic patients in the outpatient setting, however there is emerging data to suggest that complement inhibitors may be an effective rescue therapy in acute myasthenic exacerbation or crisis. Methods We present two cases of non-ventilator-dependent patients with refractory or recurrent myasthenic exacerbation in whom eculizumab was used as a rescue therapy, review the literature to date on inpatient use of complement inhibitor therapy for myasthenic crisis/exacerbation, and discuss the pathophysiology underlying rapid clinical response. Results Both patients had a rapid response to eculizumab with return of ability to speak and swallow within 48 h in one patient and reduction in MG-ADL score of >6 points within 2 weeks in one patient. Both achieved minimal symptom expression (defined as MG-ADL score of 0 or 1) within weeks and had sustained response to outpatient complement inhibitor therapy. Nineteen previously published papers (58 patients) were identified. Many patients had a clinically significant reduction in MG-ADL score or other objective evidence of clinical improvement within days, and had a sustained benefit with continued outpatient therapy. Conclusions Our findings add to a growing body of literature suggesting that complement inhibition may be a useful, fast-acting therapy for myasthenic exacerbation in the inpatient setting in some cases. This rapid response is likely due to functional complement blockade in patients with complement mediated neuromuscular junction damage as a primary cause of MG exacerbation/crisis.
Neurological manifestations represent commonly persistent features of post-COVID conditions (PCC), but mechanisms underlying their pathogenesis remain unclear. In this study, participants with neuro-PCC (n = 29), mostly presenting with persistent headache, fatigue, sleep disturbances, anosmia/dysgeusia, cognitive complaints, and/or paresthesia, recovered from COVID-19 (n = 32), and non-infected controls (n = 32), all matched for sex and age, had paired serum samples from acute phase (0–14 days) and two time points of convalescence (3–6 months and 9–12 months) assessed for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), antineutrophil cytoplasmic antibodies (ANCA), and autoantibodies against cytokines using Luminex assays. Biomarkers of neuroinflammation, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total Tau protein, and neurogranin were quantified by Ella ELISA and complement activation was determined by increased C5b–9 levels. Patients with neuro-PCC showed a greater number of neurological symptoms during acute phase, with increased frequency of headache and fatigue, and a higher prevalence of obesity and cardiovascular comorbidities. GFAP remained elevated for up to one year after infection, independently of symptom persistence. However, only patients with neuro-PCC exhibited a transient increase in NfL levels during acute phase, and persistent complement activation throughout follow-up. No specific autoantibody was associated with neuro-PCC, but these patients exhibited a higher cumulative autoantibody burden. Multivariable logistic regression analysis showed that hospitalization and the neurological burden during the acute phase were associated with neuro-PCC, whereas anti-cytokine autoantibody counts showed an inverse trend. Increased complement activation and a higher autoantibody burden suggest a broad and nonspecific immune activation that may contribute to a sustained low-grade neuroinflammatory state, potentially driving the persistence of neurological symptoms after COVID-19.
