Perioperative use of eculizumab in patients with thymoma-associated myasthenia gravis: A preliminary case series of five patients - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. 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Learn more: PMC Disclaimer | PMC Copyright Notice IBRO Neurosci Rep . 2026 Mar 29;20:559–567. doi: 10.1016/j.ibneur.2026.03.011 Search in PMC Search in PubMed View in NLM Catalog Add to search Perioperative use of eculizumab in patients with thymoma-associated myasthenia gravis: A preliminary case series of five patients Yaotong Ou Yaotong Ou a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Yaotong Ou a, 1 , Yi Wen Yi Wen a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China b School of Medicine, Guangdong Medical University, Zhanjiang, China Find articles by Yi Wen a, b, 1 , Yiyi Liu Yiyi Liu a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Yiyi Liu a , Mingjun Lai Mingjun Lai a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Mingjun Lai a , Honghao Wang Honghao Wang a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Honghao Wang a , Xi Chen Xi Chen a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Xi Chen a, ⁎ , Huili Zhang Huili Zhang a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Huili Zhang a, ⁎ , Yu Peng Yu Peng a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China Find articles by Yu Peng a Author information Article notes Copyright and License information a Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China b School of Medicine, Guangdong Medical University, Zhanjiang, China ⁎ Correspondence to: Department of Neurology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, No. 1 Panfu Road, Guangzhou, China. [email protected] [email protected] 1 Yaotong Ou and Yi Wen contributed equally to this work. Received 2025 Dec 1; Accepted 2026 Mar 28; Collection date 2026 Jun. © 2026 The Authors. Published by Elsevier Inc. on behalf of International Brain Research Organization. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). PMC Copyright notice PMCID: PMC13091172 PMID: 42004615 Abstract Patients with myasthenia gravis (MG) are at risk of myasthenic crisis (MC) or clinical deterioration following thymectomy. Although eculizumab has demonstrated efficacy in the management of MC, its role in perioperative optimization for thymectomy in MG patients has not been systematically evaluated. To assess the efficacy of eculizumab in the perioperative management of thymectomy in MG patients, we included five patients with MG who received perioperative eculizumab treatment during thymectomy. Clinical features and perioperative data were comprehensively analyzed. Outcomes were assessed using the Quantitative Myasthenia Gravis (QMG), MG-Activities of Daily Living (MG-ADL), and Clinical Absolute Scores (CAS). Additionally, we measured acetylcholine receptor antibody (AChR-Ab) levels, total hemolytic complement (CH50), immunoglobulin G (IgG) concentrations, and lymphocyte subset percentages. In this study, from baseline to pre-surgery, all patients except patient 2 and patient 5 exhibited a reduction in QMG and CAS scores; Patients 2 and 5 showed no changes in MG-ADL scores, whereas Patients 1, 3, and 4 all demonstrated clinical improvement with reduced scores. All patients demonstrated decreased CH50 levels, fluctuating AChR-Ab levels and IgG levels. The thymectomy was performed smoothly, and the tracheal tube was removed promptly after surgery. No exacerbation of MG symptoms, postoperative myasthenic crisis (POMC), or serious complications occurred within 7 days post-surgery. In conclusion, these preliminary findings suggest that perioperative eculizumab may provide a feasible strategy for reducing the risk of POMC in MG patients. As a hypothesis-generating case series, further large-scale prospective studies are warranted to confirm these observations. Keywords: Thymectomy, Myasthenia gravis (MG), Postoperative myasthenic crisis (POMC), Eculizumab Highlights • Perioperative eculizumab may prevent postoperative myasthenic crisis in high-risk MG. • Terminal complement inhibition achieved clinical stability with no serious complications. • QMG and CAS scores improved, correlating with decreased CH50 levels during therapy. • Individualized dosing protocols successfully managed patients with varying risk profiles. 1. Introduction Myasthenia gravis (MG) is an autoimmune disorder caused by antibody-mediated disruption of neuromuscular transmission, primarily due to autoantibodies targeting acetylcholine receptors, specifically acetylcholine receptor antibodies (AChR-Ab) ( Shelly, 2025 ). Thymectomy is a common procedure performed in patients with MG, particularly those with thymomas or in cases of generalized MG that are refractory to medication ( Wolfe et al. 2016 ). However, the physiological stress response induced by surgery poses a significant challenge in patients with unstable MG, as it may exacerbate symptoms and precipitate a =MC ( Ando et al. 2015 ). Currently, plasmapheresis/plasma exchange (PLEX) and intravenous immunoglobulin (IVIG) are widely used to minimize perioperative symptom exacerbation and prevent MC. Nevertheless, both therapies have limitations. Although plasmapheresis may reduce the risk of MC in the postoperative period, its benefit is limited in patients with mild disease expression ( Reis et al. 2019 ). In addition, it can cause extracorporeal circuit coagulation, leading to treatment delays and increased nursing workload ( Ren et al. 2024 ), and carries the risk of catheter-related infections ( Hou et al. 2024 ). PLEX is also associated with potential adverse effects such as hypocalcemia, allergic reactions, and hypotension, and it entails significant costs ( François et al., 2023 , Landfeldt et al., 2020 ). IVIG can help alleviate MC symptoms to some extent ( Dalakas and Meisel, 2022 ); however, its cost and limited accessibility pose barriers to routine perioperative use, raising questions about its cost-effectiveness. Therefore, alternative treatment strategies are needed to ensure safe perioperative management following thymectomy. Eculizumab, a recombinant humanized monoclonal antibody, specifically inhibits terminal complement activation, thereby protecting neuromuscular junctions from immune-mediated injury. The REGAIN study and its extension demonstrated that eculizumab significantly improves clinical scores and disease severity in patients with refractory generalized MG (gMG) ( Mantegazza et al. 2021 ). It can also serve as a rapid-acting therapy to relieve MG symptoms and prevent exacerbations ( Menacher et al. 2024 ). Furthermore, real-world data suggest that eculizumab is effective in achieving symptom control and reducing corticosteroid use in patients with non-thymomatous myasthenia gravis ( Jin et al. 2024 ). However, clinical experience regarding its use during the perioperative period of thymectomy remains limited. In this preliminary case series, we report our observations on the use of eculizumab for perioperative management in five patients with thymoma-associated myasthenia gravis (TAMG) undergoing thymectomy. Our goal is to provide preliminary insights into the potential role of eculizumab in optimizing surgical outcomes and maintaining clinical stability in this high-risk population. 2. Methods 2.1. Ethics approval and consent to participate All procedures involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and the Declaration of Helsinki, including its later amendments or comparable ethical standards (Approval No. K-2025–010–01, approved on 15 January 2025). Prior to the administration of eculizumab, participants were thoroughly informed about its potential efficacy and adverse events, and the purpose and details of the treatment were fully explained. 2.2. Patients This prospective single-center study was conducted at local Hospital, from February 2025 to April 2025. The inclusion criteria were as follows: (1) Age ≥ 18 years; (2) presence or history of thymoma; (3) MG patients with AChR antibody-positive fulfilling the 2020 international consensus or Chinese diagnostic guidelines; (4) ability to understand and fully cooperate with the study procedures. The exclusion criteria were: (1) patients with non-thymomatous myasthenia gravis; (2) poor general condition or unstable vital signs, and (3) incomplete medical history. 2.3. Perioperative Eculizumab infusion protocol Eculizumab (900 mg) was administered intravenously as a perioperative adjunct to ensure clinical stability. Surgical Timing and Readiness Criteria: The timing of thymectomy was individualized based on the patient's clinical response to the initial eculizumab infusion. Readiness for surgery was determined by a multidisciplinary team (MDT) consisting of neurologists, thoracic surgeons, and anesthesiologists. Surgery was scheduled once a stable and safe preoperative condition was achieved, defined by: 1) a reduction of ≥ 2 points points in QMG score from baseline, or 2) a decrease of ≥ 2 points in the MG-ADL score. These thresholds represent a clinically meaningful improvement ( Mantegazza et al. 2021 ). The primary therapeutic goal was to achieve Myasthenia Gravis Foundation of America (MGFA) classes I and II of surgery, without the development of new bulbar or respiratory symptoms. For patients who did not meet these criteria after the initial infusion, additional doses were administered at weekly intervals until the readiness threshold was met. Patients 1, 2, 3, and 5 achieved surgical readiness after a single infusion and thus followed a two-dose regimen (one preoperative and one postoperative dose). Patient 4, however, presented with relatively mild symptoms at baseline, which posed a challenge for achieving the predefined scoring reduction. Despite this, a second preoperative dose was administered to ensure maximal terminal complement blockade before the surgical stress of thymectomy, eventually achieving the required scoring threshold. Unlike other patients who received a single preoperative dose, Patient 4 received two preoperative infusions (900 mg each) to achieve the required clinical threshold. The MDT reasoned that this intensive preoperative loading provided sufficient terminal complement blockade. Given her mild baseline symptoms and continued clinical stability post-extubation, the team opted to omit the postoperative dose to avoid potential over-treatment, prioritizing individualized pharmacotherapy based on cumulative preoperative drug exposure. 2.4. Clinical data collection and outcome assessments A comprehensive set of perioperative data was recorded, including demographics, surgical indicators, and clinical outcomes. Clinical Severity Assessments: Disease severity was evaluated at three critical time points: (1) Baseline (on admission); (2) Pre-surgery (one day prior to surgery, following 1–2 sessions of eculizumab treatment); and (3) Post-surgery Day 4 (D4). Outcomes were quantified using the Quantitative Myasthenia Gravis (QMG) score, the MG-Activities of Daily Living (MG-ADL) scale, and the Clinical Absolute Scores (CAS). Laboratory and Immunological Indices: To monitor the biological response to eculizumab and surgical stress, serum indices and immunological profiles were measured at Baseline, Pre-surgery, Post-surgery Day 1 (D1), and D4. These included acetylcholine receptor antibody (AChR-Ab) concentrations, total hemolytic complement activity (CH50), immunoglobulin G (IgG) levels, and the percentages of lymphocyte subsets. 3. Results 3.1. Baseline clinical features The baseline characteristics of the five patients are summarized in Table 1 . The cohort consisted of two males (P1, P3) and three females (P2, P4, P5). The mean age was 45.6 ± 10.8 years (n = 5). The average disease duration before thymectomy was 34.8 ± 33.7 months. All patients were seropositive for AChR-Ab, with a mean baseline concentration of 7.66 ± 2.32 nmol/L. All patients were diagnosed with thymomas based on preoperative imaging and postoperative pathology. Table 1. Clinical and demographic features of the patients. Patient No. 1 2 3 4 5 Gender Male Female Male Female Female Age (years) 27 45 53 51 52 BMI 24.65 21.64 25.78 24.35 24.39 Disease duration (months) 15 72 72 3 12 MG subtype gMG gMG gMG gMG gMG Antibody type AChR-Ab AChR-Ab AChR-Ab AChR-Ab AChR-Ab Presence of thymoma Y Y Y Y Y Admission MGFA IIIA IIA IIB IIB IIA Comorbidities N Bronchiectasis N N N Other autoimmune disorders (no/yes) N N N N N Preoperative history of myasthenic crisis (no/yes) Y Y Y N N History of tumor metastasis N Y N N N Preoperative bulbar symptoms Y N N N N Preoperative daily dose of pyridostigmine bromide (mg) 60 0 180 180 120 Past immunotherapy Pred, Tac, Efgartigimod Pred, MMF Pred, CsA, Tac, Plex, Efgartigimod, Eculizumab N Pred, Tac ECG Sinus rhythm; Occasional atrial premature beats Sinus rhythm; Shortened PR interval Sinus rhythm; Occasional atrial premature beats; Frequent ventricular premature beats with short-run ventricular tachycardia Sinus rhythm; flattened T-waves in leads V4–V6 Sinus rhythm; Normal electrocardiogram Medications for anxiety Sertraline, Zolpidem N Trazodone, Escitalopram Oxalate Alprazolam N Max vital capacity (L) 5.15 3.12 3.69 2.51 2.7 FEV 1 (L) 4.17 2.62 2.90 2.07 2.22 FVC (L) 4.92 3.05 3.56 2.45 2.62 FEV 1 /FVC (%) 83.44 83.98 83.94 84.37 84.19 MVV (L/min) 146.46 99.87 110.93 87.07 90.18 DLCOc-SB (mmol/min/kPa/L) 7.07 8.36 8.19 11.41 7.39 Albumin-to-globulin ratio 2.1 1.2 1.5 1.6 1.7 Open in a new tab BMI, body mass index; gMG: generalized myasthenia gravis; AChR-Ab: acetylcholine receptor antibody; MGFA: Myasthenia Gravis Foundation of America; Pred: Prednisone; Tac: Tacrolimus; MMF: Mycophenolate Mofetil; CsA: Cyclosporin A; Plex: Plasma Exchange; ECG: Electrocardiogram; FEV 1 : Forced expiratory volume in the first second; FVC: Forced vital capacity; MVV: Maximal Voluntary Ventilation; DLCOc-SB: Diffusion lung capacity for carbon monoxide—corrected Single Breath; Y: yes; N: no; NA: not available. The MGFA classification at admission was IIIA for P1, IIA for P2, P5, and IIB for P3, P4. None of the patients had significant medical comorbidities except for P2, who had bronchiectasis. Three patients had a history of at least one MC, and P2 had previously experienced POMC following an earlier surgical intervention. Four patients were on maintenance therapy with oral corticosteroids and immunosuppressants at the time of admission. Notably, P3 had received eculizumab infusions eight months prior to the current surgery to manage an MC episode. Regarding preoperative respiratory function, P4 and P5 exhibited a maximum vital capacity below 2.9 L. Preoperative psychological assessment identified anxiety in three patients, for whom anti-anxiety treatment was prescribed. The albumin-to-globulin (A/G) ratio was within the normal range for all patients except for P2. 3.2. Surgery-related indicators The surgical data for the five patients is presented in Table 2 . Three patients underwent video-assisted thoracoscopic surgery, while the other two underwent open thoracotomy. The duration of surgery ranged from 55 to 185 min. Blood loss was minimal in all cases, with a maximum volume of 50 mL. All tumors had long axes exceeding 50 mm, and one tumor was adherent to the pericardium. The thymomas were primarily classified as World Health Organization (WHO) histological type B3, as seen in P2, P3, and P4. Table 2. Information related to surgery and anesthesia. Patient No. 1 2 3 4 5 Surgical procedure VAST Thoracotomy VAST Thoracotomy VAST Operation time (min) 55 157 95 110 185 Intraoperative blood loss (mL) 10 50 5 10 20 Intraoperative findings N Myocardial adhesion N N N Thymoma size (mm) 50 × 32 × 24 52 × 43 × 25 65 × 40 × 20 60 × 50 × 30 50 × 40 × 20 Thymic pathology Mixed B1/B2 B3 Mixed B2/B3 B3 B1 ASA score III III III III III NYHA Functional Classification II II I I I Anesthesia time (min) 115 225 170 175 250 Rocuronium administered (mg) 45 50 55 55 50 Sugammadex administered (mg) 200 0 200 200 200 Postoperative analgesia pump Y Y Y Y Y Open in a new tab VAST, video-assisted Thoracic Surgery; ASA: American Society of Anesthesiologists; NYHA: New York Heart Association; Y: yes; N: no. All patients underwent thymoma resection for the first time, except for P2, who had a complex surgical history involving three separate interventions. Her initial surgery consisted of thymoma resection combined with excision of masses in the left upper lung and chest wall, followed by adjuvant radiotherapy and chemotherapy postoperatively. Five years postoperatively, she presented with a retroperitoneal mass, pathologically confirmed as metastatic type B3 thymic carcinoma. After initially opting for conservative management, a recurrence of the thymic tumor two months later necessitated a second surgical intervention. Notably, P2 had no prior MG symptoms or MG-specific medication until one month after her second surgery, when she developed a MC requiring intensive care unit (ICU) admission and mechanical ventilation (MV). She was subsequently managed with long-term oral corticosteroids and immunosuppressants. Following her third surgery (the current intervention stabilized by eculizumab), no further MC or symptom exacerbation was observed. 3.3. Postoperative-related parameters The postoperative data for the five patients is shown in Table 3 . All patients were transferred to the ICU for standardized monitoring and comprehensive management following thymectomy. No major postoperative complications, such as pleural effusion, pulmonary infection, or cardiac events, were observed. Table 3. Postoperative related information. Patient No. 1 2 3 4 5 Postoperative myasthenic crisis N N N N N Nerve palsy N N N N N Pericarditis N N N N N Atelectasis N N N N N Postoperative lung infection N N N N N Incision infection N N N N N Pleural effusion N N N N N Postoperative mortality N N N N N Duration of MV (min) 150 350 95 1410 1500 Duration of postoperative intubation (h) 1.83 4.92 2.42 22.50 23.25 Length of ICU stay (h) 18.5 25 22 23.83 45 Days with drainage tube after operation 4 5 2 3 3 Drainage volume over first 3 days (mL) 395 380 200 505 650 Postoperative hospital stays (days) 6 13 9 12 12 Status at discharge Independent Independent Independent Independent Independent Open in a new tab MV, Mechanical Ventilation; ICU: Neurology Critical Care Unit; N: no. The duration of MV ranged from 95 to 1500 min. The mean duration of postoperative intubation for the cohort was 10.98 h. The length of the ICU stay was approximately 1 day except for P5. All patients had chest tube drainage for less than 5 days, with drainage volumes below 650 mL within the first 72-h after surgery. As shown in Table 4 , none of the patients developed postoperative hypercapnia (PaCO₂ retention). Adequate oxygenation was maintained in most cases, with PaO₂/FiO₂ ratios exceeding 300 in four patients; notably, Patient 5 exhibited a lower PaO₂/FiO₂ ratio of 233, which remained clinically manageable without requiring prolonged ventilation. Ventilator settings indicated a favorable recovery of postoperative respiratory function. All patients met the predefined criteria for extubation, and endotracheal tubes were successfully removed within a standardized timeframe. Fig. 1. Open in a new tab Preoperative contrast-enhanced chest CT imaging. Representative scans reveal thymomas in all five patients prior to surgical intervention. Table 4. Respiratory-related parameters. Patient No. 1 2 3 4 5 RASS score 0 -1 0 0 0 SpO 2 (%) 99 100 100 100 100 pO 2 (mmHg) 126 285 203 228 105 pH 7.47 7.36 7.35 7.44 7.40 *Increase in PaCO 2 (mmHg) -9 -1 2 -1 -7 Pulse (bpm) 126 61 100 78 75 Systolic blood pressure 171 132 138 143 109 Respiratory rate (breaths/min) 18 18 16 13 17 PaO₂/FiO₂ 341 695 495 556 233 Open in a new tab RASS: Richmond Agitation - Sedation Scale. * An Increase in PaCO 2 refers to the difference between the following two-time points: immediately after intensive care unit admission and immediately before extubation. 3.4. Clinical outcome assessments throughout the perioperative course The longitudinal changes in clinical scores for the five patients are illustrated in Fig. 2 . From Baseline to Pre-surgery: Following the initiation of eculizumab treatment, Patients 1, 3, and 4 exhibited meaningful reductions in both QMG and CAS scores. In contrast, Patients 2 and 5, who presented with lower baseline scores (near the "floor effect"), maintained stable QMG and CAS levels. Regarding MG-ADL scores, Patient 1, 3, and 4 demonstrated clinical improvement, while Patients 2 and 5 showed no change from their baseline scores of zero. Notably, for Patient 4, the administration of a second preoperative dose resulted in further stabilization of her clinical status prior to surgery ( Fig. 2 ). Fig. 2. Open in a new tab Longitudinal clinical trajectories of MG severity and scores in five patients. The primary timeline of the perioperative period, illustrating the timing of admission (Baseline), eculizumab infusions (indicated by star) and surgical intervention, overlaid with the longitudinal changes in QMG scores(A). Changes in MG-ADL(B), CAS(C) scores across the same critical time points: Baseline, pre-surgery (Day −1), and postoperative day 4 (D4). Note: The baseline refers to the patient's admission time. Since these time vary for different patients, the starting number of days are different. From Pre-surgery to Post-surgery D4: All five patients maintained clinical stability during the immediate postoperative period. QMG scores remained stable or showed slight continued improvement in all cases. Notably, Patients 3 and 4 showed further meaningful improvements in their MG-ADL scores by D4, whereas scores for the remaining patients remained stable at low levels. CAS scores remained consistently stable across the cohort, with no patients experiencing symptom exacerbation or emotional distress following the surgical intervention. 3.5. Longitudinal changes in serum and immunological indices The dynamic changes in serum indices are illustrated in Fig. 3 . From baseline to the pre-surgical period, a rapid and significant decline in CH50 levels was observed in all five patients, confirming the effective systemic activity of eculizumab in inhibiting terminal complement activation. AChR-Ab levels exhibited individualized fluctuations; while most patients remained relatively stable, Patient 2 showed a marked increase on D1 that persisted through D4. IgG levels fluctuated slightly within the normal range for all patients (excluding P1, for whom only baseline data were available). Fig. 3. Open in a new tab Dynamics of immunological markers and complement activity. Changes in AChR-Ab, CH50, and IgG levels in all patients at baseline, pre-surgery, D1, and D4. The changes in lymphocyte subsets across the perioperative period are illustrated in Fig. 4 . CD3 + CD4 + T cells showed a transient decrease on D1 across the cohort (notably starting from pre-surgery in Patient 2), followed by a recovery toward baseline by D4. CD3 + CD8 + T cells remained relatively stable in most cases, though a brief decline on D1 was noted in Patients 3 and 4. Regarding CD3 – CD19 + B cells, most patients exhibited minimal fluctuations, although Patient 2 showed a marked increase on D1 that persisted through D4. Finally, CD16 + CD56 + natural killer (NK) cells demonstrated a characteristic transient elevation on D1 in three patients (excluding Patient 1 and 5), with all cases trending back toward baseline by D4 Fig. 4. Open in a new tab Changes in lymphocyte subsets across the perioperative period. Repeated measurements of lymphocyte percentage at baseline, pre-surgery, D1, and D4. 4. Discussion In this study, we reported on five patients with TAMG who underwent thymectomy with perioperative eculizumab therapy. Notably, three patients (P1, P2, and P3) had a documented history of MC, a recognized risk factor for POMC ( Mantegazza et al. 2021 ). Contrary to these expectations, no patients in our cohort developed POMC or experienced symptom exacerbation within the first month post-surgery. Three out of five patients had a documented history of MC, further underscoring the high-risk nature of this study population. While we acknowledge the confounding potential of long-term immunosuppression and multidisciplinary care in these complex patients, the presence of recurrent MC history is widely recognized as a major predictor for postoperative respiratory failure. The successful prevention of POMC in these specifically identified “crisis-prone” individuals suggests that terminal complement inhibition may offer an additional layer of stability that complements traditional intensive management. This consistency across a cohort with such significant clinical frailty provides preliminary evidence that our protocol is applicable to the most challenging TAMG cases encountered in clinical practice. Particularly noteworthy is P2, who previously required mechanical ventilation for POMC following her second thoracotomy. The fact that such a high-risk, refractory patient achieved a complication-free recovery under the current protocol suggests that terminal complement blockade remains effective even in sensitized clinical settings. Thus, her inclusion enhances the clinical relevance of our findings by demonstrating eculizumab’s potential in high-risk prophylactic scenarios. Ultimately, our results suggest that eculizumab, alongside meticulous multidisciplinary care, may provide a vital stabilizing effect during the vulnerable perioperative window. We explicitly acknowledge that the diverse regimen of concomitant immunosuppressants (including corticosteroids, tacrolimus, MMF, and CsA) and prior therapies (PLEX and efgartigimod) in our cohort creates a complex pharmacological background. This polypharmacy, necessitated by the patients' high-risk clinical status, makes it impossible to isolate the individual therapeutic contribution of eculizumab in a controlled manner. Patient 3 had previously received eculizumab. The fact that eculizumab maintained its stabilizing effect in P3 during the perioperative window suggests that prior responsiveness may serve as a reliable predictor for surgical safety. In rare disease research, documenting such longitudinal, reproducible efficacy in high-risk scenarios provides essential, albeit preliminary, evidence for clinical decision-making. Preoperative anxiety or depression has been reported in approximately 22.5% of patients ( Li et al. 2022 ). Anxiety can exacerbate autonomic dysfunction and hinder respiratory muscle recovery ( Chen et al. 2024 ), and it has been shown to negatively affect perioperative outcomes ( Zou et al. 2016 ). Despite this, the identification and management of preoperative anxiety are often overlooked in clinical settings. The favorable outcomes in our cohort may be influenced by multidisciplinary perioperative optimization, including the management of preoperative anxiety. In our cohort, three patients received anxiolytics, which likely synergized with complement inhibition to prevent autonomic-driven exacerbations. Furthermore, multiple studies have identified several significant risk factors for POMC, including thoracotomy approach, WHO histological classification B2–B3 thymoma ( Liu et al. 2020 ), preoperative vital capacity < 2.9 L ( Chigurupati et al. 2018 ), low preoperative A/G ratio ( Wei et al. 2023 ), ASA physical status classification of ≥ 2 ( Jiao et al. 2023 ), and a history of respiratory disease ( Torrini et al. 2021 ). These established risk factors indicate that our five patients were at considerable risk of postoperative clinical deterioration, POMC, or prolonged MV. However, contrary to these predictions, none of the patients developed POMC or experienced clinical deterioration within 1 month following surgery. In addition to rigorous preoperative management and meticulous perioperative care, the temporal stabilization observed in all five high-risk patients provides preliminary evidence for eculizumab as a potential prophylactic adjunct. Nevertheless, whether this favorable outcome is attributable to the incorporation of eculizumab into perioperative care requires further investigation in large-scale studies. The study proposes the following extubation criteria for postoperative patients with MG: clear consciousness; adequate gas exchange (SpO₂ >85–90%; PaO₂ >50–60 mmHg, pH >7.32; PaCO₂ increase <10 mmHg from baseline), hemodynamic stability (heart rate <120–140 bpm; systolic blood pressure <180–200 mmHg), and a stable ventilatory pattern (respiratory rate <30–35 breaths/min) ( Leuzzi et al. 2014 ). All patients in our cohort met these criteria and underwent successful extubation without complications. The mean duration of postoperative intubation was 10.98 h, and the average ICU stay was approximately 26.9 h. In comparison, Saeteng et al. reported a mean postoperative intubation time of 29 h and an ICU stay of 55.2 h ( Saeteng et al. 2013 ). The shorter durations observed in our cohort may reflect differences in perioperative management strategies, postoperative care protocols, and ICU nursing practices across institutions. P2 demonstrated a unique pattern of AChR-Ab dynamics, with an immediate postoperative increase on D1. The phenomenon of AChR-Ab levels rebounding beyond pretreatment baseline levels after transient reduction, known as “antibody overshoot” ( Ching et al. 2021 ), is typically seen in patients receiving plasmapheresis or immunomodulatory therapies (e.g., FcRn inhibitors such as efgartigimod) and often correlates with clinical deterioration ( Kawama et al. 2023 ). In this study, P2 exhibited an overshoot phenomenon following eculizumab administration. However, unlike previous reports, this patient showed no symptomatic worsening, as assessed through serial QMG and ADL scores and close AchR-Ab titer monitoring. The dissociation between AChR-Ab “overshoot” and clinical stability in P2 highlights the potent terminal complement blockade provided by eculizumab. Even with increased circulating autoantibodies, the inhibition of the membrane attack complex (MAC) effectively protected the neuromuscular junction from functional impairment. For CD3 – CD19 + B cells, four patients showed minimal changes, while Patient 2 exhibited an increased level following thymectomy. Yu et al. reported a significant decrease in regulatory B-cell proportions after thymectomy ( Yu et al. 2024 ), which contrasts with our observed total B-cell dynamics—a discrepancy likely attributable to differences in the specific B-lymphocyte subsets measured. Notably, Patient 2 displayed elevated total B-cell levels on D4 compared to baseline, which may suggest either (i) thymectomy-mediated disruption of peripheral immune tolerance or (ii) surgery-induced proinflammatory cytokine surges that promote B-cell activation ( Kooshesh et al. 2023 ). Regarding CD16 + CD56 + NK cells, individualized response patterns were observed. While most patients (P2, P3, and P4) showed a characteristic transient elevation on D1 followed by a return to baseline, Patient 1 maintained relatively stable levels, and Patient 5 exhibited a progressive decline throughout the perioperative period. This variability contrasts with the findings of Schoenberg et al., who reported a uniform postoperative dip in NK-cell levels ( Schoenberg et al. 2023 ). Despite these differing temporal trajectories, our findings suggest that terminal complement inhibition might modulate the immediate post-surgical innate immune response, a hypothesis that warrants further investigation. The AGR remained within the normal range in all patients except for P2, whose value was < 1.42 ± 0.26. AGR is a reliable indicator of systemic inflammation. Wei et al. found that patients with POMC exhibited significantly lower preoperative AGR values (mean ± SD: <1.42 ± 0.26) compared to patients without POMC ( Wei et al. 2023 ). Although P2’s markedly reduced AGR of 1.2 would typically indicate a higher risk of POMC, no such complications occurred, potentially due to our novel perioperative eculizumab prophylaxis protocol. Longitudinal monitoring and studies involving larger sample sizes are necessary to clarify the clinical significance of these findings. 5. Conclusion In conclusion, this preliminary case series suggests that individualized perioperative use of eculizumab in high-risk patients with thymoma-associated myasthenia gravis may facilitate clinical stabilization and reduce the risk of POMC. However, the inherent limitations of this study—including the small sample size (n = 5), the non-comparative design, and the limited follow-up duration—preclude definitive conclusions regarding efficacy. Future large-scale, randomized controlled trials are essential to validate these preliminary findings and establish eculizumab's role in the standardized perioperative management of MG. CRediT authorship contribution statement Yaotong Ou: Writing – review & editing, Writing – original draft. Yi Wen: Writing – review & editing, Writing – original draft. Yiyi Liu: Investigation. Mingjun Lai: Validation, Data curation. Honghao Wang: Conceptualization. Xi Chen: Visualization. Huili Zhang: Methodology, Funding acquisition. Yu Peng: Supervision, Project administration. Compliance with ethical standards This study was conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. Funding This study was supported by National Natural Science Foundation of China (No. 82001333). Conflicts of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Contributor Information Xi Chen, Email: [email protected]. Huili Zhang, Email: [email protected]. Data availability The datasets generated and analyzed during the current study include clinical patient information and are therefore not publicly available. De-identified data may be made available from the corresponding author upon reasonable request. References Ando T., Omasa M., Kondo T., Yamada T., Sato M., Menju T., Aoyama A., Sato T., Chen F., Sonobe M., Date H. Predictive factors of myasthenic crisis after extended thymectomy for patients with myasthenia gravis. Eur. J. Cardiothorac. Surg. 2015;48(5):705–709. doi: 10.1093/ejcts/ezu530. 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