That blind spot is the post-operative patient. Fernández argues that in patients with poorly controlled gMG who undergo urgent abdominal surgery—say, emergency laparotomy for perforated diverticulitis—myasthenic or cholinergic crisis is too often treated as a diagnosis of exclusion rather than a condition demanding immediate priority intervention once clinically suspected. In practice, respiratory failure in this population is frequently labeled as multifactorial, attributed to sepsis, fluid overload, or post-operative deconditioning, rather than recognized as myasthenic crisis. The problem, she stresses, is not uncertainty about whether crisis belongs in the differential diagnosis; it is diagnostic ambiguity that delays crisis-specific therapy while clinicians sequentially rule out competing explanations.

The immunological logic behind the risk is layered. Immunosuppression can mask both clinical and septic signs, blunting the early warning signals that would normally trigger suspicion. Infection itself can drive autoantibody production, with single-cell immune profiling studies showing that neutrophils promote myasthenia gravis exacerbation through secretion of B-cell activating factor (BAFF). Prolonged fasting around surgery creates nutritional deficits, including hypophosphatemia, which directly impairs diaphragmatic contractility and is further aggravated by refeeding syndrome. Sepsis-related oxidative stress adds yet another hit, damaging the motor endplate where antibodies are already compromising signal transmission. Each mechanism compounds the others, and none announces itself clearly in a sedated, ventilated patient.

The confounders specific to the post-operative setting are formidable. Sedation and pain mask the oculobulbar signs—ptosis, diplopia, bulbar weakness—that typically herald a myasthenic crisis. Post-operative ileus introduces uncertainty about whether orally administered pyridostigmine is even being absorbed, complicating the distinction between myasthenic crisis, in which antibody-mediated weakness predominates, and cholinergic crisis, caused by excess anticholinesterase medication. And the growing number of patients maintained on biologic therapy raises a thorny question: does plasma exchange (PLEX) remain appropriate as first-line rescue in someone already receiving an FcRn antagonist or other biologic agent?

Fernández also challenges a widespread assumption embedded in the literature the review cites: that oculobulbar findings will accompany or precede respiratory failure, prompting early suspicion of crisis. In her clinical experience, myasthenic crisis in the critically ill post-operative patient can present as isolated hypercapnic respiratory failure with no oculobulbar signs at all. In an intubated patient on mechanical ventilation, cooperation-dependent pulmonary function testing is simply not feasible. Her proposed solution is bedside diaphragmatic ultrasonography, a rapid, repeatable tool that can support or exclude the suspicion of crisis without delaying management, and she argues it deserves explicit consideration in future guidance on crisis recognition in post-operative intensive care units.

At the heart of the commentary lies what Fernández calls the central clinical dilemma: the sequencing of exclusion versus treatment. The instinctive pattern—rule out fluid overload, uncontrolled sepsis, cholinergic excess, and mechanical or pulmonary causes before committing to crisis-specific immunotherapy—may be exactly backwards. Pure fluid overload rarely accounts on its own for the need for intubation; one would expect a response to diuretics and non-invasive ventilation, together with a distinct lung ultrasound pattern such as that described in the BLUE protocol. Moreover, the two mechanisms are not mutually exclusive, since respiratory muscle weakness can amplify even mild fluid overload. In a patient with poorly controlled gMG on biologic therapy and acute hypercapnic respiratory failure of neuromuscular pattern in the early post-operative period, the pretest probability of crisis is high enough that treatment should start in parallel with, not subordinate to, the exclusion of alternative diagnoses.

The emerging evidence base for acting quickly is thin but consistent. A systematic review by Tang and colleagues describes improvement with efgartigimod across 20 patients with myasthenic crisis, and a prospective case series by Song and colleagues reports ventilator weaning within a mean of 10.4 days. Adding weight to the argument for early intervention, absence of myasthenia gravis-specific immunosuppressive treatment at intensive care unit admission has been independently associated with prolonged weaning in a WEAN Safe analysis of ventilation outcomes. Together, Fernández contends, these findings support initiating specific treatment without delay, even while acknowledging that efgartigimod’s crisis evidence remains limited to case series rather than randomized trials.

The question of PLEX versus FcRn antagonism in patients already on biologic therapy, Fernández argues, deserves nuance rather than a blanket recommendation. Efgartigimod itself, by inhibiting FcRn, non-specifically reduces circulating IgG, which may also accelerate clearance of IgG-based therapeutic monoclonal antibodies—so it should not be assumed that efgartigimod better preserves concomitant biologic therapy than PLEX does. Biologic agents in gMG are also mechanistically heterogeneous. For B-cell-depleting agents such as rituximab, PLEX matters most shortly after infusion; once B-cell depletion is established, the pharmacodynamic effect may persist even as circulating drug levels fall. Complement inhibitors such as eculizumab and ravulizumab, by contrast, depend on continuous plasma concentrations, so lowering circulating levels—whether by PLEX or by FcRn inhibition—could more directly compromise their efficacy. Her commentary proposes a decision framework weighing hemodynamic and coagulation status, sepsis control, renal and volume status, and the specific biologic agent, since no single dimension alone determines the safest rescue choice.

Looking ahead, Fernández calls on future guidance to address three priorities explicitly: recognition of myasthenic crisis in patients whose post-operative respiratory failure is otherwise labeled multifactorial after urgent abdominal surgery; the role of diaphragmatic ultrasonography in atypical presentations lacking oculobulbar signs; and individualization of rescue therapy by biologic agent, mechanism, and timing, without implying superiority of any single modality in myasthenic crisis. As more patients with difficult-to-control gMG are maintained on biologic therapy, the population of immunosuppressed surgical patients facing this diagnostic minefield is set to grow, making the commentary’s message—that crisis should be treated in parallel with exclusion, not after it—one that intensive care and neurology teams alike cannot afford to ignore.

Subject of Research: Efgartigimod therapy and myasthenic crisis recognition in generalized myasthenia gravis

Article Title: Commentary: Efgartigimod for generalized myasthenia gravis: a comprehensive review of clinical evidence and future perspectives

Article References: Fernández, A. B. (2026). Commentary: Efgartigimod for generalized myasthenia gravis: a comprehensive review of clinical evidence and future perspectives. Frontiers in Neurology, 17, Article 1975630. https://doi.org/10.3389/fneur.2026.1975630

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1975630

Keywords: efgartigimod, generalized myasthenia gravis, myasthenic crisis, FcRn antagonist, plasma exchange, diaphragmatic ultrasonography, post-operative respiratory failure, neuromuscular disorders, Commentary, generalized, myasthenia, gravis