Prognostic Biomarkers in Guillain-Barré Syndrome: Lymphocyte-Based Ratio and Albumin Level

Prognostic Biomarkers in Guillain-Barré Syndrome: Lymphocyte-Based Ratio and Albumin Level | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic Biomarkers in Guillain-Barré Syndrome: Lymphocyte-Based Ratio and Albumin Level Eun Kyoung Lee, Sooyoung Kim, Eunhee Sohn This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8784464/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Guillain–Barré syndrome (GBS) is an acute immune-mediated polyneuropathy with a variable clinical course. Early identification of patients at risk for respiratory failure or poor functional outcomes remains challenging. This study aimed to evaluate the prognostic value of clinical features and readily available serologic biomarkers, with a particular focus on lymphocyte-based inflammatory ratios and serum albumin levels. Methods We retrospectively analyzed 126 patients diagnosed with GBS who were admitted to Chungnam National University Hospital between January 2012 and January 2022. Baseline clinical characteristics, neurological findings, and laboratory parameters—including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein-to-albumin ratio (CAR), and serum albumin levels—were assessed within 24 hours of admission. Serum albumin levels at two weeks after immunotherapy were collected when available. Disease severity and long-term outcomes were evaluated using the Hughes score. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify prognostic factors for respiratory failure and poor long-term outcomes. Results Among 126 patients (mean age 54.8 ± 16.3 years), 19 (15.1%) developed respiratory failure and 23 (18.2%) had poor functional outcomes at 3 months. Baseline NLR was significantly higher in patients with respiratory failure and was associated with a 1.4-fold increased risk in the unadjusted model (OR = 1.4; 95% CI = 1.1–1.8; p = 0.007). Lower baseline serum albumin levels were associated with poor long-term outcomes. Persistently low serum albumin levels at two weeks after immunotherapy were independently associated with both respiratory failure and poor long-term outcomes. ROC analysis demonstrated that serum albumin levels at two weeks showed good predictive performance for poor outcomes (AUC = 0.818). Conclusions Early inflammatory markers and serum albumin levels provide complementary prognostic information in patients with GBS. Elevated NLR at admission may help identify patients at risk for respiratory failure, while persistently low serum albumin levels after treatment are strongly associated with adverse long-term outcomes. These readily available biomarkers may facilitate early risk stratification and guide timely clinical management in GBS. Guillain–Barré syndrome biomarkers prognosis neurtrophil-to-lymphocyte ratio albumin Figures Figure 1 Figure 2 1. Introduction Guillain-Barre syndrome (GBS) is a representative immune-mediated inflammatory polyneuropathy that occurs acutely after infection. In 60–70% of patients, limb paralysis progresses rapidly within a few days to weeks after respiratory or gastrointestinal infection. In most patients, symptoms peak within two weeks [ 1 ]. The plateau phase lasts from days to months, and symptoms are gradually improved over several months or years [ 2 – 3 ]. When treated appropriately, 60–80% of patients recover to the point of being able to walk within 6 months, but 20% of patients require intensive care unit treatment due to respiratory paralysis and severe autonomic dysfunction, and 5% of patients have expired. Therefore, immediate and proper management is needed [ 4 – 5 ]. Several clinical factors, including advanced age (> 40 years), requirement for mechanical ventilation, and the presence of systemic infection (especially diarrhea), have been reported as prognostic indicators in patients with GBS [ 6 – 7 ]. In addition to these clinical parameters, laboratory biomarkers-such as neutrophil-lymphocyte ratio (NLR), serum creatine kinase level, and serum albumin levels-have also been associated with disease severity and clinical outcome [ 8 – 9 ]. Among these biomarkers, serum albumin has received particular attention. Fokkink WR et. al. reported that hypoalbuminemia measured two weeks after intravenous immunoglobulin (IVIG) treatment was associated with a more severe clinical course and poorer outcomes, including respiratory failure and inability to walk [ 10 ]. However, serum albumin levels assessed two weeks after treatment may be substantially influenced by intercurrent medical conditions and may be too late to allow early prediction of respiratory failure [ 11 ]. Therefore, serum albumin levels have limitations as a biomarker for rapid prognostic assessment during the acute phase of GBS and highlighting the need for reliable biomarkers at an earlier stage. Consistent with this concept, another study evaluated the prognostic value of serum inflammatory markers, including the NLR, C-reactive protein, and serum albumin levels, in patients with GBS [ 12 – 13 ]. This study demonstrated that serum albumin was the only marker independently associated with clinical outcomes at the time of hospital discharge [ 12 – 13 ]. Nevertheless, the prognostic significance of serologic biomarkers in GBS remains controversial. Therefore, we conducted this study to identify clinical features and serologic biomarkers that may aid in predicting prognosis in patients with GBS. Specifically, we aimed to evaluate the utility of neurological assessments and routinely obtained serologic markers at initial admission for early identification of patients at risk for respiratory failure and poor outcomes, thereby facilitating timely and aggressive management. 2. Materials and Methods 2.1 Patients and Clinical Data We retrospectively analyzed the data from patients diagnosed with GBS who visited Chungnam National University Hospital from January 2012 to January 2022. Electrodiagnostic studies were analyzed at least two serial examinations within a month of onset according to the electrodiagnostic criteria described by Uncini et al [ 14 ]. Patients were classified in consensus with three experienced neurologists: acute motor axonal neuropathy (AMAN), acute inflammatory demyelinating polyneuropathy (AIDP), Miller Fisher syndrome (MFS), and the unspecified group. Patients with chronic inflammatory demyelinating polyneuropathy (CIDP), autoimmune disease, malignancy, and active systemic infection at the time of admission were excluded. Patients receiving hormonal or immunosuppressive agents that affect the immune function as well as those with hematologic disease, renal disorders, or hepatic disorders, were also excluded. Clinical variables including age, sex, time from symptom onset to nadir, length of hospitalization, Hughes score at the nadir and 3 months after admission, and treatment modality were assessed. Antecedent events, such as respiratory tract infection, gastrointestinal infection, surgery, or vaccination within 4 weeks of symptom onset, were also reviewed. The specific clinical symptoms are defined as follows. Sensory symptoms were characterized by the presence of paresthesia or numbness. Bulbar symptoms included the presence of dysarthria or dysphagia. Delayed facial palsy was defined as the occurrence of facial palsy while other symptoms were stable or improving. Severe pain was defined as persistent pain despite the use of two or more neuropathic pain medications. 2.2 Laboratory assessment Baseline laboratory parameters were assessed using blood samples obtained within 24 hours of admission. They included serum albumin level, C-reactive protein (CRP), neutrophil count, lymphocyte count, and monocyte count. The neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) and CRP to albumin ratio (CAR) were subsequently calculated. All laboratory assessments were performed prior to the administration of immunotherapies. The NLR was defined as the ratio of neutrophil count to lymphocyte count, the MLR as the ratio of monocyte count to lymphocytes, and the CAR as the ratio of CRP level to serum albumin level. Serum albumin levels measured 2 weeks after treatment were collected when available. To compare biologic marker levels between patients with GBS and healthy individuals, data from age- and sex-matched healthy controls who visited the hospital’s health care center were collected. White blood cell (WBC), neutrophil count, lymphocyte count, monocyte count and albumin levels were obtained from these control subjects. 2.3 Classification according to the disease status and long-term prognosis The Hughes score was evaluated at the nadir point and at 3 months after admission as follows; grade 0, healthy; grade 1, minor signs and symptoms, able to run; grade 2, able to walk independently; grade 3, able to walk with a walker or support; grade 4, bed- or chair-bound; grade 5, assisted respiration required for at least part of the day; and grade 6, death [ 15 ]. Baseline severity and long-term outcomes were evaluated using the Hughes score at nadir and at the 3 months follow-up, respectively. Severe disease was defined by a nadir Hughes score ≥ 3. Poor long-term outcome was defined as a Hughes score ≥ 3 at the 3-month follow-up. Furthermore, patients were categorized into the respiratory failure group if endotracheal intubation was required at any point during the treatment course. We then compared clinical features and laboratory parameters among groups stratified by baseline severity, long-term outcome, and the presence or absence of respiratory failure. 2.4 Statistical analysis All statistical analyses were performed using the IBM SPSS Statistics for Windows (version 26.0; IBM Corp., Armonk, N.Y., United States). Statistics for the clinical variables are presented as proportions, means ± standard deviation (SD), and ranges. The independent t-test, Pearson’s chi-squared test, Fisher’s exact test, Mann–Whitney U test, and correlation analysis were used to compare the statistical significance between the groups. Logistic regression analysis was performed to determine the predictive factors for GBS, and we calculated odds ratios (ORs) and their respective 95% confidence intervals (CIs). Propensity score matching was performed to compare the median values ± standard deviation for laboratory parameters between patients with GBS and matched healthy controls. The receiver operating characteristic curve (ROC) analysis was performed to evaluate the cut-off values, sensitivity, and specificity of the biomarkers in predicting poor prognosis. Statistical significance was set at p < 0.05. 3. Results 3.1 Patient demographics and clinical features A total 126 patients were included in this study. The mean age of the 126 patients with GBS was 54.8±16.3 years, and the male-to-female ratio was 1.9 to 1.0 (Table 1). A preceding event was identified in 104 cases (82.5%). The most common preceding events were gastrointestinal infection (46%), followed by respiratory infection (39.7%) and surgery (0.8%). Among the patients, 103 (81.7%) were treated with a single course of intravenous immunoglobulin (IVIG), 9 patients (7.1%) received two courses of IVIG. The second course was administered after one month due to treatment failure, defined as lack of improvement following the initial administration. Ten patients (7.9%) received both IVIG and steroids. Two patients did not receive immunotherapy because of mild symptoms. The most common accompanying symptom was sensory symptoms (74.6%), followed by bulbar dysfunction (34.9%), severe pain (24.6%), and delayed facial palsy (7.9%) (Figure 1). As shown in Figure 1, bulbar dysfunction was associated with statistically significant differences in disease severity, respiratory failure, and long-term outcomes (all p < 0.05). Electrodiagnostic subtypes were categorized as follows: AMAN in 45 patients (35.7%), AIDP in 33 patients (26.2%), MFS in 22 patients (17.5%), and unspecified in 26 patients (20.6%) (Table 1). Patients were further stratified into three subgroups according to baseline disease severity, respiratory failure, and long-term outcome (Table 1). Regarding baseline severity, 91 patients (72.2%) presented with a severe baseline disease status, and 19 patients (15.1%) had respiratory failure. At the 3-month follow-up, 23 patients (18.2%) were unable to walk independently and were consequently classified into the poor prognosis group. The mean interval from symptom onset to IVIG administration for the 126 patients was 4.6±3.2 days. Notably, treatment was initiated more rapidly in the respiratory failure group and the poor long-term outcome group. Excluding two patients who did not receive immunotherapy due to minor symptoms, all patients received acute-phase treatment, indicating that therapy was initiated relatively soon after the onset of symptoms. 3.2. Serological comparison between patients with GBS and health controls Serological variables of 126 patients with GBS and 2910 health controls (HCs) are compared in Table 2. The median values of WBC count, neutrophil count, lymphocyte count, monocyte count, NLR, and MLR were significantly higher in patients with GBS than in HCs. Serum albumin levels were significantly lower in patients with GBS compared with HCs. 3.3. Serological parameters associated with prognosis Laboratory parameters stratified by prognostic groups are presented in Table 3. Baseline serum albumin levels were obtained within 24 hours of admission for all 126 patients, and follow-up measurements at two weeks were available for 81 patients. Lower baseline serum albumin levels were significantly associated with poor long-term outcomes. Moreover, persistently low serum albumin levels at two weeks were significantly associated with both respiratory failure and poor long-term outcomes. There were no significant differences in CRP and CAR values between the three groups. However, NLR values were significantly elevated in patients with respiratory failure and poor long-term outcome. In contrast, MLR showed an association with poor long-term outcome, and cerebrospinal fluid (CSF) total protein levels showed significantly high levels only in patients with severe baseline disease, but did not show any association with respiratory failure and long-term outcome (Table 3). 3.4 Prognostic factors for respiratory failure and long-term outcome Logistic regression analysis (both unadjusted and adjusted models) was performed to identify factors associated with respiratory failure and long-term outcomes in GBS patients (Table 4). In the unadjusted model, the NLR was associated with a 1.4-fold higher risk of respiratory failure (OR=1.4; 95% CI=1.1-1.8; p=0.007). However, this association did not remain statistically significant in the adjusted model. Baseline albumin levels were significantly associated with long-term outcomes in the unadjusted model. Importantly, albumin levels measured at 2 weeks were statistically significantly associated with both respiratory failure and long-term outcomes in both models. 3.5 Receiver operating characteristic curve (ROC) analysis of biomarkers ROC analysis was performed to identify the cutoff values of NLR and albumin level at 2 weeks for predicting respiratory failure and long-term prognosis in GBS patients, and evaluate their respective sensitivity and specificity (Figure 2). For the prediction of respiratory failure, the optimal cutoff value of NLR was 3.552, showing a sensitivity of 68.4%, and a specificity of 71.9%. The area under the curve (AUC) was 0.675. The optimal cutoff value for the albumin level at 2 weeks for predicting long-term outcome was 3.55 mg/dL, showing a sensitivity of 73.9%, and a specificity of 77.6%. The AUC for albumin was 0.818, significantly higher than that of the NLR model. 4. Discussion In this study, we investigated the role of clinical features and serological parameters as prognostic biomarkers for baseline disease status, respiratory failure, and long-term outcome in patients with GBS. With respect of clinical manifestations, patients presenting with bulbar symptoms, delayed facial palsy, and severe pain demonstrated a significantly greater baseline disease severity. In particular, the presence of bulbar symptoms was both associated with respiratory failure and poor long-term outcomes (Table 1). This is consistent with previous reports, which also demonstrated that bulbar symptoms were significantly associated with both baseline severity and mechanical ventilation [ 11 , 16 ]. Among the serologic markers, NLR was significantly higher in patients with GBS than in healthy controls, and elevated NLR in the early stage of the disease was identified as a risk factor for respiratory failure. This finding suggests that NLR may primarily reflect the intensity of the acute inflammatory response rather than mechanisms directly related to axonal damage or long-term functional recovery. In patients with GBS, it has been hypothesized that circulating white blood cells might proliferate and migrate, causing inflammatory recruitment to peripheral nerves and triggering the development of GBS, but the exact pathogenesis remains unclear [ 17 – 18 ]. Inflammatory factors such as neutrophils, lymphocytes, and monocytes play an important role in triggering the innate immune response during the induction phase of systemic inflammation and are involved in inducing autoimmunity against host tissue after infection. Although their role has not been fully studied, increased neutrophil counts in patients with infections such as Campylobater jejuni are thought to contribute to the pathogenesis of GBS by releasing chemokines, cytokines, and adhesion molecules that disrupt the blood-nerve barrier. In postmortem studies and animal experiments have shown that the spinal nerve roots of the motor and sensory nerves are extensively infiltrated by inflammatory cells, including T cells and macrophages, accompanied by segmental demyelination and axonal degeneration [ 19 ]. Previous studies have shown that abnormal NLR is associated with autoimmune diseases. High NLR levels have been shown to have prognostic value for disease activity in primary Sjogren’s syndrome [ 20 ], systemic lupus erythematous (SLE) [ 21 ], and Behcet’s disease [ 22 ], and have been reported to be associated not only with these rheumatic diseases but also with central nervous system demyelinating disease such as autoimmune encephalitis [ 23 ], neuromyelitis optica, and multiple sclerosis [ 24 – 26 ]. In a study of GBS patients, it was also reported to be a prognostic factor for severe GBS and mechanical ventilation [ 27 ]. A study reported that NLR is considered a non-specific prognostic parameter, but it has diagnostic value as a poor prognostic factor at 4 weeks [ 28 ]. CAR also have been reported as a prognostic biomarker of GBS in some studies [ 29 ]. Notably, previous studies have reported no significant differences in inflammatory biomarkers according to GBS subtype [ 30 ]. In a previous study, comparisons of NLR, platelet-to-lymphocyte ratio, CRP, and serum albumin levels among AMAN, AMSAN, and AIDP subtypes revealed no intergroup differences, although these markers were correlated with disease severity [ 30 ]. This is consistent with the findings of the present study. A recent meta-analysis evaluating nine studies assessed the prognostic value of NLR in patients with GBS [ 31 ]. Among these, three studies reported specific cutoff values. The first study, conducted in 35 patients, identified a cutoff of 4.40; the second, in 117 patients, reported 3.05; and the third, which enrolled the largest cohort of 426 patients, determined a cutoff of 3.5 [ 31 ]. In our study, involving 126 patients, the optimal cutoff value of NLR for predicting respiratory failure was 3.552, with a sensitivity of 68.4% and a specificity of 71.9%. This finding is consistent with the third study, which also focused on respiratory failure as the primary outcome. It is noteworthy that the first two studies used poor functional outcome, defined as Hughes score ≥ 3, as their endpoint, whereas the third study targeted respiratory failure. In contrast, our study stratified patients into three groups—disease severity, respiratory failure, and poor outcome—and compared clinical and serologic markers across these categories. Importantly, we demonstrated that the association between NLR and respiratory failure in the early stage of the disease was statistically more significant than with other outcome measures. To our knowledge, this is the first study to highlight the stronger predictive value of NLR for respiratory failure in GBS patients, thereby underscoring its potential utility as a clinically relevant biomarker for early risk stratification. In contrast to NLR, serum albumin levels were associated with long-term outcomes. Low serum albumin levels in early stage suggest poor long-term outcomes, and persistently low albumin levels at 2 weeks were a poor prognostic factor for both respiratory failure and long-term outcomes [ 32 – 34 ]. These findings suggest that serum albumin reflects not only acute inflammatory burden but also ongoing systemic and microvascular dysfunction [ 35 ]. Consistent with our results, previous reports have demonstrated that albumin levels correlate with the clinical outcome of GBS. Anjum J et. al. demonstrated that low baseline albumin levels were significantly associated with greater disease severity (Hughes Score), increased need for intensive care and mechanical ventilation, and delayed recovery [ 36 ]. This is because albumin is extravasated due to increased permeability of capillaries, and their synthesis is reduced, with increased catabolism after severe inflammatory disease [ 37 ]. In addition, serum albumin acts as a powerful antioxidant by inhibiting free hydroxyl radicals generated during inflammation, demyelination, and axonal damage [ 38 – 39 ]. This study has several limitations. First, because of the retrospective design of the study in a tertiary center, the sample size was small, and clinical features, including sensory symptoms and predisposing factors, could be insufficient. And we could not exclude all factors that would affect serum biomarkers. Second, NLR was assessed only at a single time point. Planned serial NLR measurements might provide additional prognostic information, particularly for long-term outcomes. Third, the prevalence of AMAN in Eastern Countries such as Korea and Japan have higher rates than those in Western countries. Further studies involving diverse populations are necessary. Forth, serum albumin levels at two weeks were not available for all patients, which may have introduced selection bias. Finally, if we examine other immune cells and factors simultaneously, it could help identify prognostic factors and understand the pathophysiology of GBS. 5. Conclusion In this study, an elevated NLR was associated with a 1.4-times higher risk of respiratory failure (95% CI = 1.1–1.8, p = 0.007). In addition, lower serum albumin levels measured at 2 weeks after treatment were significantly associated with a higher risk of both respiratory failure and poor long-term outcomes. As a factor to predict GBS Patients who are likely to require mechanical ventilation due to respiratory failure, it would be advisable to check the NLR level at admission and the serum albumin levels 2 weeks after. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Chungnam National University Sejong Hospital (approval number: 2026–02–003–001). The requirement for informed consent was not required from the participants in accordance with the national legislation and institutional requirements. Consent for publication Not applicable Competing interests The authors have no conflicts of interest to declare. Acnowledgements Not applicable Funding This research was supported by the Chungnam National University Hospital Research Fund, 2022. Author Contribution E.K.L., S.K., and E.S. contributed to the study design. S.K. and E.S. were responsible for data collection. E.K.L., S.K., and E.S. were responsible for data analysis. E.K.L. and E.S. wrote and critically revised several versions of the manuscript. All authors have read and approved the final version of the manuscript. Data Availability Data will be made available upon reasonable request to the corresponding author. References Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barre syndrome. Lancet. 2016;388(10045):717–27. Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain-Barre syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671–83. Ying Wang WL, Zhang Y, Ma X. Chunkui Zhou and Hong-Liang Zhang. Long-term prognosis of Guillain-Barré syndrome not determined by treatment options? Oncotarget. 2017;8(45). Finsterer J. Triggers of Guillain-Barre Syndrome: Campylobacter jejuni Predominates. Int J Mol Sci. 2022;23(22). François Fourrier LR, Jean-François Hurtevent S, Spagnolo. A simple functional marker to predict the need for prolonged mechanical ventilation in patients with Guillain-Barré syndrome. Crit Care. 2011;15:R65. Inés González-Suárez IS-G. Francisco Javier Rodríguez de Rivera and Javier Arpa. Guillain-Barré Syndrome: Natural history and prognostic factors: a retrospective review of 106 cases. BMC Neurol. 2013;13:95. Khedr EM, Mohamed MZ, Shehab MMM. The early clinical and laboratory predictors of GBS outcome: hospital-based study, Assiut University, Upper Egypt. Egypt J Neurol Psychiatry Neurosurg. 2023;59(1). Jahan I, Ahmed R, Ahmed J, Khurshid S, Biswas PP, Upama IJ, et al. Neutrophil-lymphocyte ratio in Guillain-Barre syndrome: A prognostic biomarker of severe disease and mechanical ventilation in Bangladesh. J Peripher Nerv Syst. 2023;28(1):47–57. Lee EK, Kim S, Jo N, Sohn E. Association between hyperCKemia and axonal degeneration in Guillain-Barre syndrome. BMC Neurol. 2023;23(1):92. Fokkink WR, Walgaard C, Kuitwaard K, Tio-Gillen AP, van Doorn PA, Jacobs BC. Association of Albumin Levels With Outcome in Intravenous Immunoglobulin-Treated Guillain-Barre Syndrome. JAMA Neurol. 2017;74(2):189–96. Kim SHSA, Mcclave SA, Martindale RG, Miller KR, Hunt RT. Hypoalbuminemia and Clinical Outcomes: What is the Mechanism behind the Relationship? Am Sur. 2017;83(11). Tunc A. Early predictors of functional disability in Guillain-Barre Syndrome. Acta Neurol Belg. 2019;119(4):555–9. Ethemoglu O, Calik M. Effect of serum inflammatory markers on the prognosis of adult and pediatric patients with Guillain-Barre syndrome. Neuropsychiatr Dis Treat. 2018;14:1255–60. Uncini A, Kuwabara S. The electrodiagnosis of Guillain-Barre syndrome subtypes: Where do we stand? Clin Neurophysiol. 2018;129(12):2586–93. Wang Y, Shang P, Xin M, Bai J, Zhou C, Zhang HL. The usefulness of chief complaints to predict severity, ventilator dependence, treatment option, and short-term outcome of patients with Guillain-Barre syndrome: a retrospective study. BMC Neurol. 2017;17(1):200. Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005;366(9497):1653-66. Steinbach K, Piedavent M, Bauer S, Neumann JT, Friese MA. Neutrophils amplify autoimmune central nervous system infiltrates by maturing local APCs. J Immunol. 2013;191(9):4531-9. Hagen KM, Ousman SS. The Neuroimmunology of Guillain-Barre Syndrome and the Potential Role of an Aging Immune System. Front Aging Neurosci. 2020;12:613628. Hu ZD, Sun Y, Guo J, Huang YL, Qin BD, Gao Q, et al. Red blood cell distribution width and neutrophil/lymphocyte ratio are positively correlated with disease activity in primary Sjogren's syndrome. Clin Biochem. 2014;47(18):287 – 90. Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio(NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016;26(3):372-6. Lee YH, Song GG. Neutrophil-to-lymphocyte ratio, mean platelet volume and platelet-to-lymphocyte ratio in Behcet's disease and their correlation with disease activity: A meta-analysis.Int J Rheum Dis. 2018;21(12):2180-7. Yu Y, Wu Y, Cao X, Li J, Liao X, Wei J, et al. The Clinical Features and Prognosis of Anti-NMDAR Encephalitis Depends on Blood Brain Barrier Integrity. Mult Scler Relat Disord. 2021;47:102604. Xie H, Zhao Y, Pan C, Zhang J, Zhou Y, Li Y, et al. Association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of first attack neuromyelitis optica spectrum disorder(NMOSD): a retrospective cohort study. BMC Neurol. 2021;21(1):389. Carnero Contentti E, Delgado-Garcia G, Criniti J, Lopez PA, Pettinicchi JP, Cristiano E, et al. An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD. Front Immunol. 2021;12:628024. Fahmi RM, Ramadan BM, Salah H, Elsaid AF, Shehta N. Neutrophil-lymphocyte ratio as a marker for disability and activity in multiple sclerosis. Mult Scler Relat Disord.2021;51:102921. Sharshar T, Chevret S, Bourdain F, Raphaël J. Early predictors of mechanical ventilation in Guillain-Barré syndrome. Crit Care Med. 2003;31(1). Sutantoyo FF, Fadil, Basuki M, Fidiana, Hamdan M. Correlation Between Neutrophil-to-Lymphocyte Ratio and Motoric Deterioration in Patients With Guillain-Barre Syndrome. J Clin Neurol.2022;18(6):671 – 80. Ning P, Yang B, Yang X, Huang H, Shen Q, Zhao Q, et al. Clinical value of C-reactive protein/albumin ratio in Guillain-Barre syndrome. Neurol Sci. 2021;42(8):3275-83. Paneyala S NA, Iyer M, Gopi A. Assessment of Serum Inflammatory Markers and their Correlation with Clinical Severity and Electrophysiological Subtypes of Guillain Barre Syndrome, and Investigating their Use as Prognostic Markers of Guillain Barre Syndrome.Ann Indian Acad Neurol. 2024;27(1):101-3. Cabanillas-Lazo M, Quispe-Vicuna C, Cruzalegui-Bazan C, Pascual-Guevara M, Mori-Quispe N, Alva-Diaz C. The neutrophil-to-lymphocyte ratio as a prognostic biomarker in Guillain-Barre syndrome: a systematic review with meta-analysis. Front Neurol. 2023;14:1153690. Di X, Wang J, Li L, Liu L. Establishment of a single-center-based early prognostic scoring system for Guillain-Barre syndrome. BMC Neurol. 2023;23(1):97. Hussain J, Saqib M, Sohailkhan, Jan F, Marwat S, Khan N. Determine Serum Albumin as an Independent Biomarker for Clinical Outcome in Plasmapheresis Treated GBS Patients Pakistan Journal of Medical & Health Sciences. 2021;15(2). Shalman A, Savir S, Mechnik Steen Y, Ovanyan A, Boniel N, Koyfman L, et al. Albumin levels as a biomarker for second Intravenous Immunoglobulin (IVIG) treatment in Guillain-Barre syndrome (GBS). J Clin Neurosci. 2020;74:247-9. Grelowska M, Logon K, Dziadkowiak E. Prognostic factors associated with worse outcomes in patients with GBS: A systematic review. Adv Clin Exp Med. 2025;34(3):457 – 67. Anjum J, Rehman MAU, Nazir H, Mengal M, Dina TJ, Das D. Serum Albumin as an Independent Indicator in Guillain-Barre Syndrome Patients Undergoing Plasmapheresis. Jounal of Population Therapeutics & Clinical Pharmacology. 2025;32(6):1755-62. Badshah M, Shabbir G, Nabi SF, Ahmed D. Association of serum albumin levels and guillain barre syndrome (gbs) outcome. Pakistan Journal of Neurological Sciences.2018;13(2). Rabi R, Alsaid RM, Matar AN, Dawabsheh Y, Abu Gaber D. The role of serum albumin in critical illness, predicting poor outcomes, and exploring the therapeutic potential of albumin supplementation. Sci Prog. 2024;107(3):368504241274023. Atrash AK, de Vasconcellos K. Low albumin levels are associated with mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit. South Afr J Crit Care. 2020;36(2). Tables Table 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Table2.docx Table3.docx Table4.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 11 May, 2026 Reviewers agreed at journal 09 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers invited by journal 19 Feb, 2026 Editor invited by journal 16 Feb, 2026 Editor assigned by journal 13 Feb, 2026 Submission checks completed at journal 13 Feb, 2026 First submitted to journal 04 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8784464","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":594847869,"identity":"a25a936e-f385-466e-93ef-06a3442ff6c2","order_by":0,"name":"Eun Kyoung Lee","email":"","orcid":"","institution":"Chungnam National University Sejong Hospital","correspondingAuthor":false,"prefix":"","firstName":"Eun","middleName":"Kyoung","lastName":"Lee","suffix":""},{"id":594847870,"identity":"943a38df-d3ae-41ca-a825-138d13e11467","order_by":1,"name":"Sooyoung Kim","email":"","orcid":"","institution":"Chungnam National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sooyoung","middleName":"","lastName":"Kim","suffix":""},{"id":594847871,"identity":"b0c2ee2e-b40e-4790-be0d-485dc9dcc384","order_by":2,"name":"Eunhee Sohn","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYDACCQYGZhDNDyISCkjRItkA0mJAihaDA2CSCB380u0PHxfuuJNvfH514ocHBgzy/GIH8GuRnHPG2HjmmWeW22683SwBdJjhzNkJ+LUY3Mhhk+ZtO2xgduPsBpCWBIPbBLTY30h/BtZiPOPs5h9EaTGQSDADazHg791GnC0SN3KMjUFaJG7wbrNIMJAg7Bf+GekPH4O08Pef3XzzR4WNPL80AS1I9oFVShCrHGzfAVJUj4JRMApGwUgCACcOQk7eALvQAAAAAElFTkSuQmCC","orcid":"","institution":"Chungnam National University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Eunhee","middleName":"","lastName":"Sohn","suffix":""}],"badges":[],"createdAt":"2026-02-04 09:38:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8784464/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8784464/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103506766,"identity":"502505f6-7269-4083-8659-7b8b64b8cc0f","added_by":"auto","created_at":"2026-02-26 13:39:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27686,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClassification of disease severity by clinical symptoms\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/b077565b9e71777eb8171dc8.png"},{"id":103346432,"identity":"393e08e3-dc37-4e5f-9b9c-ed855eb36457","added_by":"auto","created_at":"2026-02-24 16:21:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":76265,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReceiver operating characteristic curve (ROC) analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReceiver operating characteristic curve (ROC) analysis of the prognostic value of the serum albumin level at 2 weeks after treatment for long-term outcomes (A), and neutrophil-lymphocyte ratio(NLR) for respiratory failure (B) in patients with GBS. The optimal cut-offs for albumin_2 and NLR were 3.55 and 3.552, respectively\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/b5ba82e0ea8517eba889eb42.png"},{"id":103509941,"identity":"7db09ce6-06b8-4c34-b9c3-7c5ca814ae93","added_by":"auto","created_at":"2026-02-26 14:02:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":777517,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/faa60e0e-1603-4486-a4d9-258a13ae0143.pdf"},{"id":103346433,"identity":"83b45ef5-c58d-4590-89c8-8774a052e2ac","added_by":"auto","created_at":"2026-02-24 16:21:48","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":29620,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/593b389e56d2d8806aa651de.docx"},{"id":103346434,"identity":"0f39b5ce-7252-4143-be75-93138f5b7278","added_by":"auto","created_at":"2026-02-24 16:21:49","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":17582,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/d3d7dee8ec0e690b5569d0de.docx"},{"id":103346435,"identity":"bdb3f478-dc80-42ed-95dc-2bbc191ec2d9","added_by":"auto","created_at":"2026-02-24 16:21:49","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":22059,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/2fc5889b6a0d6e1f6bc94ed8.docx"},{"id":103346436,"identity":"c9a45eff-fe89-46d8-af4d-2b30ef006fca","added_by":"auto","created_at":"2026-02-24 16:21:49","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":21135,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8784464/v1/2ff85d234f5aa7223ab70527.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Biomarkers in Guillain-Barré Syndrome: Lymphocyte-Based Ratio and Albumin Level","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eGuillain-Barre syndrome (GBS) is a representative immune-mediated inflammatory polyneuropathy that occurs acutely after infection. In 60\u0026ndash;70% of patients, limb paralysis progresses rapidly within a few days to weeks after respiratory or gastrointestinal infection. In most patients, symptoms peak within two weeks [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The plateau phase lasts from days to months, and symptoms are gradually improved over several months or years [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. When treated appropriately, 60\u0026ndash;80% of patients recover to the point of being able to walk within 6 months, but 20% of patients require intensive care unit treatment due to respiratory paralysis and severe autonomic dysfunction, and 5% of patients have expired. Therefore, immediate and proper management is needed [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral clinical factors, including advanced age (\u0026gt;\u0026thinsp;40 years), requirement for mechanical ventilation, and the presence of systemic infection (especially diarrhea), have been reported as prognostic indicators in patients with GBS [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition to these clinical parameters, laboratory biomarkers-such as neutrophil-lymphocyte ratio (NLR), serum creatine kinase level, and serum albumin levels-have also been associated with disease severity and clinical outcome [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong these biomarkers, serum albumin has received particular attention. Fokkink WR et. al. reported that hypoalbuminemia measured two weeks after intravenous immunoglobulin (IVIG) treatment was associated with a more severe clinical course and poorer outcomes, including respiratory failure and inability to walk [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, serum albumin levels assessed two weeks after treatment may be substantially influenced by intercurrent medical conditions and may be too late to allow early prediction of respiratory failure [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Therefore, serum albumin levels have limitations as a biomarker for rapid prognostic assessment during the acute phase of GBS and highlighting the need for reliable biomarkers at an earlier stage.\u003c/p\u003e \u003cp\u003eConsistent with this concept, another study evaluated the prognostic value of serum inflammatory markers, including the NLR, C-reactive protein, and serum albumin levels, in patients with GBS [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This study demonstrated that serum albumin was the only marker independently associated with clinical outcomes at the time of hospital discharge [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Nevertheless, the prognostic significance of serologic biomarkers in GBS remains controversial.\u003c/p\u003e \u003cp\u003eTherefore, we conducted this study to identify clinical features and serologic biomarkers that may aid in predicting prognosis in patients with GBS. Specifically, we aimed to evaluate the utility of neurological assessments and routinely obtained serologic markers at initial admission for early identification of patients at risk for respiratory failure and poor outcomes, thereby facilitating timely and aggressive management.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patients and Clinical Data\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed the data from patients diagnosed with GBS who visited Chungnam National University Hospital from January 2012 to January 2022. Electrodiagnostic studies were analyzed at least two serial examinations within a month of onset according to the electrodiagnostic criteria described by Uncini et al [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Patients were classified in consensus with three experienced neurologists: acute motor axonal neuropathy (AMAN), acute inflammatory demyelinating polyneuropathy (AIDP), Miller Fisher syndrome (MFS), and the unspecified group.\u003c/p\u003e \u003cp\u003ePatients with chronic inflammatory demyelinating polyneuropathy (CIDP), autoimmune disease, malignancy, and active systemic infection at the time of admission were excluded. Patients receiving hormonal or immunosuppressive agents that affect the immune function as well as those with hematologic disease, renal disorders, or hepatic disorders, were also excluded.\u003c/p\u003e \u003cp\u003eClinical variables including age, sex, time from symptom onset to nadir, length of hospitalization, Hughes score at the nadir and 3 months after admission, and treatment modality were assessed. Antecedent events, such as respiratory tract infection, gastrointestinal infection, surgery, or vaccination within 4 weeks of symptom onset, were also reviewed.\u003c/p\u003e \u003cp\u003eThe specific clinical symptoms are defined as follows. Sensory symptoms were characterized by the presence of paresthesia or numbness. Bulbar symptoms included the presence of dysarthria or dysphagia. Delayed facial palsy was defined as the occurrence of facial palsy while other symptoms were stable or improving. Severe pain was defined as persistent pain despite the use of two or more neuropathic pain medications.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Laboratory assessment\u003c/h2\u003e \u003cp\u003eBaseline laboratory parameters were assessed using blood samples obtained within 24 hours of admission. They included serum albumin level, C-reactive protein (CRP), neutrophil count, lymphocyte count, and monocyte count. The neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) and CRP to albumin ratio (CAR) were subsequently calculated. All laboratory assessments were performed prior to the administration of immunotherapies.\u003c/p\u003e \u003cp\u003eThe NLR was defined as the ratio of neutrophil count to lymphocyte count, the MLR as the ratio of monocyte count to lymphocytes, and the CAR as the ratio of CRP level to serum albumin level. Serum albumin levels measured 2 weeks after treatment were collected when available.\u003c/p\u003e \u003cp\u003eTo compare biologic marker levels between patients with GBS and healthy individuals, data from age- and sex-matched healthy controls who visited the hospital\u0026rsquo;s health care center were collected. White blood cell (WBC), neutrophil count, lymphocyte count, monocyte count and albumin levels were obtained from these control subjects.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Classification according to the disease status and long-term prognosis\u003c/h2\u003e \u003cp\u003eThe Hughes score was evaluated at the nadir point and at 3 months after admission as follows; grade 0, healthy; grade 1, minor signs and symptoms, able to run; grade 2, able to walk independently; grade 3, able to walk with a walker or support; grade 4, bed- or chair-bound; grade 5, assisted respiration required for at least part of the day; and grade 6, death [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBaseline severity and long-term outcomes were evaluated using the Hughes score at nadir and at the 3 months follow-up, respectively. Severe disease was defined by a nadir Hughes score\u0026thinsp;\u0026ge;\u0026thinsp;3. Poor long-term outcome was defined as a Hughes score\u0026thinsp;\u0026ge;\u0026thinsp;3 at the 3-month follow-up. Furthermore, patients were categorized into the respiratory failure group if endotracheal intubation was required at any point during the treatment course. We then compared clinical features and laboratory parameters among groups stratified by baseline severity, long-term outcome, and the presence or absence of respiratory failure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using the IBM SPSS Statistics for Windows (version 26.0; IBM Corp., Armonk, N.Y., United States). Statistics for the clinical variables are presented as proportions, means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), and ranges. The independent t-test, Pearson\u0026rsquo;s chi-squared test, Fisher\u0026rsquo;s exact test, Mann\u0026ndash;Whitney U test, and correlation analysis were used to compare the statistical significance between the groups. Logistic regression analysis was performed to determine the predictive factors for GBS, and we calculated odds ratios (ORs) and their respective 95% confidence intervals (CIs).\u003c/p\u003e \u003cp\u003ePropensity score matching was performed to compare the median values\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for laboratory parameters between patients with GBS and matched healthy controls. The receiver operating characteristic curve (ROC) analysis was performed to evaluate the cut-off values, sensitivity, and specificity of the biomarkers in predicting poor prognosis. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Patient demographics and clinical features\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total 126 patients were included in this study. The mean age of the 126 patients with GBS was 54.8\u0026plusmn;16.3 years, and the male-to-female ratio was 1.9 to 1.0 (Table 1). A preceding event was identified in 104 cases (82.5%). The most common preceding events were gastrointestinal infection (46%), followed by respiratory infection (39.7%) and surgery (0.8%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the patients, 103 (81.7%) were treated with a single course of intravenous immunoglobulin (IVIG), 9 patients (7.1%) received two courses of IVIG. The second course was administered after one month due to treatment failure, defined as lack of improvement following the initial administration. Ten patients (7.9%) received both IVIG and steroids. Two patients did not receive immunotherapy because of mild symptoms.\u003c/p\u003e\n\u003cp\u003eThe most common accompanying symptom was sensory symptoms (74.6%), followed by bulbar dysfunction (34.9%), severe pain (24.6%), and delayed facial palsy (7.9%) (Figure 1). As shown in Figure 1, bulbar dysfunction was associated with statistically significant differences in disease severity, respiratory failure, and long-term outcomes (all p \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eElectrodiagnostic subtypes were categorized as follows: AMAN in 45 patients (35.7%), AIDP in 33 patients (26.2%), MFS in 22 patients (17.5%), and unspecified in 26 patients (20.6%) (Table 1).\u003c/p\u003e\n\u003cp\u003ePatients were further stratified into three subgroups according to baseline disease severity, respiratory failure, and long-term outcome (Table 1). Regarding baseline severity, 91 patients (72.2%) presented with a severe baseline disease status, and 19 patients (15.1%) had respiratory failure. At the 3-month follow-up, 23 patients (18.2%) were unable to walk independently and were consequently classified into the poor prognosis group. The mean interval from symptom onset to IVIG administration for the 126 patients was 4.6\u0026plusmn;3.2 days. Notably, treatment was initiated more rapidly in the respiratory failure group and the poor long-term outcome group. Excluding two patients who did not receive immunotherapy due to minor symptoms, all patients received acute-phase treatment, indicating that therapy was initiated relatively soon after the onset of symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2. Serological comparison between patients with GBS and health controls\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerological variables of 126 patients with GBS and 2910 health controls (HCs) are compared in Table 2. The median values of WBC count, neutrophil count, lymphocyte count, monocyte count, NLR, and MLR were significantly higher in patients with GBS than in HCs. Serum albumin levels were significantly lower in patients with GBS compared with HCs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3. Serological parameters associated with prognosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLaboratory parameters stratified by prognostic groups are presented in Table 3. Baseline serum albumin levels were obtained within 24 hours of admission for all 126 patients, and follow-up measurements at two weeks were available for 81 patients. Lower baseline serum albumin levels were significantly associated with poor long-term outcomes. Moreover, persistently low serum albumin levels at two weeks were significantly associated with both respiratory failure and poor long-term outcomes.\u003c/p\u003e\n\u003cp\u003eThere were no significant differences in CRP and CAR values between the three groups. However, NLR values were significantly elevated in patients with respiratory failure and poor long-term outcome. In contrast, MLR showed an association with poor long-term outcome, and cerebrospinal fluid (CSF) total protein levels showed significantly high levels only in patients with severe baseline disease, but did not show any association with respiratory failure and long-term outcome (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Prognostic factors for respiratory failure and long-term outcome\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLogistic regression analysis (both unadjusted and adjusted models) was performed to identify factors associated with respiratory failure and long-term outcomes in GBS patients (Table 4).\u003c/p\u003e\n\u003cp\u003eIn the unadjusted model, the NLR was associated with a 1.4-fold higher risk of respiratory failure (OR=1.4; 95% CI=1.1-1.8; p=0.007). However, this association did not remain statistically significant in the adjusted model. Baseline albumin levels were significantly associated with long-term outcomes in the unadjusted model. Importantly, albumin levels measured at 2 weeks were statistically significantly associated with both respiratory failure and long-term outcomes in both models.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 Receiver operating characteristic curve (ROC) analysis of biomarkers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eROC analysis was performed to identify the cutoff values of NLR and albumin level at 2 weeks for predicting respiratory failure and long-term prognosis in GBS patients, and evaluate their respective sensitivity and specificity (Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor the prediction of respiratory failure, the optimal cutoff value of NLR was 3.552, showing a sensitivity of 68.4%, and a specificity of 71.9%. The area under the curve (AUC) was 0.675. The optimal cutoff value for the albumin level at 2 weeks for predicting long-term outcome was 3.55 mg/dL, showing a sensitivity of 73.9%, and a specificity of 77.6%. The AUC for albumin was 0.818, significantly higher than that of the NLR model.\u0026nbsp;\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this study, we investigated the role of clinical features and serological parameters as prognostic biomarkers for baseline disease status, respiratory failure, and long-term outcome in patients with GBS. With respect of clinical manifestations, patients presenting with bulbar symptoms, delayed facial palsy, and severe pain demonstrated a significantly greater baseline disease severity. In particular, the presence of bulbar symptoms was both associated with respiratory failure and poor long-term outcomes (Table\u0026nbsp;1). This is consistent with previous reports, which also demonstrated that bulbar symptoms were significantly associated with both baseline severity and mechanical ventilation [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong the serologic markers, NLR was significantly higher in patients with GBS than in healthy controls, and elevated NLR in the early stage of the disease was identified as a risk factor for respiratory failure. This finding suggests that NLR may primarily reflect the intensity of the acute inflammatory response rather than mechanisms directly related to axonal damage or long-term functional recovery.\u003c/p\u003e \u003cp\u003eIn patients with GBS, it has been hypothesized that circulating white blood cells might proliferate and migrate, causing inflammatory recruitment to peripheral nerves and triggering the development of GBS, but the exact pathogenesis remains unclear [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Inflammatory factors such as neutrophils, lymphocytes, and monocytes play an important role in triggering the innate immune response during the induction phase of systemic inflammation and are involved in inducing autoimmunity against host tissue after infection. Although their role has not been fully studied, increased neutrophil counts in patients with infections such as \u003cem\u003eCampylobater jejuni\u003c/em\u003e are thought to contribute to the pathogenesis of GBS by releasing chemokines, cytokines, and adhesion molecules that disrupt the blood-nerve barrier. In postmortem studies and animal experiments have shown that the spinal nerve roots of the motor and sensory nerves are extensively infiltrated by inflammatory cells, including T cells and macrophages, accompanied by segmental demyelination and axonal degeneration [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious studies have shown that abnormal NLR is associated with autoimmune diseases. High NLR levels have been shown to have prognostic value for disease activity in primary Sjogren\u0026rsquo;s syndrome [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], systemic lupus erythematous (SLE) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and Behcet\u0026rsquo;s disease [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and have been reported to be associated not only with these rheumatic diseases but also with central nervous system demyelinating disease such as autoimmune encephalitis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], neuromyelitis optica, and multiple sclerosis [\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In a study of GBS patients, it was also reported to be a prognostic factor for severe GBS and mechanical ventilation [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A study reported that NLR is considered a non-specific prognostic parameter, but it has diagnostic value as a poor prognostic factor at 4 weeks [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. CAR also have been reported as a prognostic biomarker of GBS in some studies [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, previous studies have reported no significant differences in inflammatory biomarkers according to GBS subtype [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In a previous study, comparisons of NLR, platelet-to-lymphocyte ratio, CRP, and serum albumin levels among AMAN, AMSAN, and AIDP subtypes revealed no intergroup differences, although these markers were correlated with disease severity [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This is consistent with the findings of the present study.\u003c/p\u003e \u003cp\u003eA recent meta-analysis evaluating nine studies assessed the prognostic value of NLR in patients with GBS [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Among these, three studies reported specific cutoff values. The first study, conducted in 35 patients, identified a cutoff of 4.40; the second, in 117 patients, reported 3.05; and the third, which enrolled the largest cohort of 426 patients, determined a cutoff of 3.5 [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In our study, involving 126 patients, the optimal cutoff value of NLR for predicting respiratory failure was 3.552, with a sensitivity of 68.4% and a specificity of 71.9%. This finding is consistent with the third study, which also focused on respiratory failure as the primary outcome. It is noteworthy that the first two studies used poor functional outcome, defined as Hughes score\u0026thinsp;\u0026ge;\u0026thinsp;3, as their endpoint, whereas the third study targeted respiratory failure. In contrast, our study stratified patients into three groups\u0026mdash;disease severity, respiratory failure, and poor outcome\u0026mdash;and compared clinical and serologic markers across these categories. Importantly, we demonstrated that the association between NLR and respiratory failure in the early stage of the disease was statistically more significant than with other outcome measures. To our knowledge, this is the first study to highlight the stronger predictive value of NLR for respiratory failure in GBS patients, thereby underscoring its potential utility as a clinically relevant biomarker for early risk stratification.\u003c/p\u003e \u003cp\u003eIn contrast to NLR, serum albumin levels were associated with long-term outcomes. Low serum albumin levels in early stage suggest poor long-term outcomes, and persistently low albumin levels at 2 weeks were a poor prognostic factor for both respiratory failure and long-term outcomes [\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. These findings suggest that serum albumin reflects not only acute inflammatory burden but also ongoing systemic and microvascular dysfunction [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConsistent with our results, previous reports have demonstrated that albumin levels correlate with the clinical outcome of GBS. Anjum J et. al. demonstrated that low baseline albumin levels were significantly associated with greater disease severity (Hughes Score), increased need for intensive care and mechanical ventilation, and delayed recovery [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. This is because albumin is extravasated due to increased permeability of capillaries, and their synthesis is reduced, with increased catabolism after severe inflammatory disease [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In addition, serum albumin acts as a powerful antioxidant by inhibiting free hydroxyl radicals generated during inflammation, demyelination, and axonal damage [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, because of the retrospective design of the study in a tertiary center, the sample size was small, and clinical features, including sensory symptoms and predisposing factors, could be insufficient. And we could not exclude all factors that would affect serum biomarkers. Second, NLR was assessed only at a single time point. Planned serial NLR measurements might provide additional prognostic information, particularly for long-term outcomes. Third, the prevalence of AMAN in Eastern Countries such as Korea and Japan have higher rates than those in Western countries. Further studies involving diverse populations are necessary. Forth, serum albumin levels at two weeks were not available for all patients, which may have introduced selection bias. Finally, if we examine other immune cells and factors simultaneously, it could help identify prognostic factors and understand the pathophysiology of GBS.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn this study, an elevated NLR was associated with a 1.4-times higher risk of respiratory failure (95% CI\u0026thinsp;=\u0026thinsp;1.1\u0026ndash;1.8, p\u0026thinsp;=\u0026thinsp;0.007). In addition, lower serum albumin levels measured at 2 weeks after treatment were significantly associated with a higher risk of both respiratory failure and poor long-term outcomes.\u003c/p\u003e \u003cp\u003eAs a factor to predict GBS Patients who are likely to require mechanical ventilation due to respiratory failure, it would be advisable to check the NLR level at admission and the serum albumin levels 2 weeks after.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e The study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Chungnam National University Sejong Hospital (approval number: 2026\u0026ndash;02\u0026ndash;003\u0026ndash;001). The requirement for informed consent was not required from the participants in accordance with the national legislation and institutional requirements.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eAcnowledgements\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was supported by the Chungnam National University Hospital Research Fund, 2022.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eE.K.L., S.K., and E.S. contributed to the study design. S.K. and E.S. were responsible for data collection. E.K.L., S.K., and E.S. were responsible for data analysis. E.K.L. and E.S. wrote and critically revised several versions of the manuscript. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData will be made available upon reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWillison HJ, Jacobs BC, van Doorn PA. Guillain-Barre syndrome. Lancet. 2016;388(10045):717\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain-Barre syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYing Wang WL, Zhang Y, Ma X. Chunkui Zhou and Hong-Liang Zhang. Long-term prognosis of Guillain-Barr\u0026eacute; syndrome not determined by treatment options? Oncotarget. 2017;8(45).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFinsterer J. Triggers of Guillain-Barre Syndrome: Campylobacter jejuni Predominates. Int J Mol Sci. 2022;23(22).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFran\u0026ccedil;ois Fourrier LR, Jean-Fran\u0026ccedil;ois Hurtevent S, Spagnolo. A simple functional marker to predict the need for prolonged mechanical ventilation in patients with Guillain-Barr\u0026eacute; syndrome. Crit Care. 2011;15:R65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIn\u0026eacute;s Gonz\u0026aacute;lez-Su\u0026aacute;rez IS-G. Francisco Javier Rodr\u0026iacute;guez de Rivera and Javier Arpa. Guillain-Barr\u0026eacute; Syndrome: Natural history and prognostic factors: a retrospective review of 106 cases. BMC Neurol. 2013;13:95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhedr EM, Mohamed MZ, Shehab MMM. The early clinical and laboratory predictors of GBS outcome: hospital-based study, Assiut University, Upper Egypt. Egypt J Neurol Psychiatry Neurosurg. 2023;59(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJahan I, Ahmed R, Ahmed J, Khurshid S, Biswas PP, Upama IJ, et al. Neutrophil-lymphocyte ratio in Guillain-Barre syndrome: A prognostic biomarker of severe disease and mechanical ventilation in Bangladesh. J Peripher Nerv Syst. 2023;28(1):47\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee EK, Kim S, Jo N, Sohn E. Association between hyperCKemia and axonal degeneration in Guillain-Barre syndrome. BMC Neurol. 2023;23(1):92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFokkink WR, Walgaard C, Kuitwaard K, Tio-Gillen AP, van Doorn PA, Jacobs BC. Association of Albumin Levels With Outcome in Intravenous Immunoglobulin-Treated Guillain-Barre Syndrome. JAMA Neurol. 2017;74(2):189\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim SHSA, Mcclave SA, Martindale RG, Miller KR, Hunt RT. Hypoalbuminemia and Clinical Outcomes: What is the Mechanism behind the Relationship? Am Sur. 2017;83(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTunc A. Early predictors of functional disability in Guillain-Barre Syndrome. Acta Neurol Belg. 2019;119(4):555\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEthemoglu O, Calik M. Effect of serum inflammatory markers on the prognosis of adult and pediatric patients with Guillain-Barre syndrome. Neuropsychiatr Dis Treat. 2018;14:1255\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUncini A, Kuwabara S. The electrodiagnosis of Guillain-Barre syndrome subtypes: Where do we stand? Clin Neurophysiol. 2018;129(12):2586\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Shang P, Xin M, Bai J, Zhou C, Zhang HL. The usefulness of chief complaints to predict severity, ventilator dependence, treatment option, and short-term outcome of patients with Guillain-Barre syndrome: a retrospective study. BMC Neurol. 2017;17(1):200.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005;366(9497):1653-66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteinbach K, Piedavent M, Bauer S, Neumann JT, Friese MA. Neutrophils amplify autoimmune central nervous system infiltrates by maturing local APCs. J Immunol. 2013;191(9):4531-9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHagen KM, Ousman SS. The Neuroimmunology of Guillain-Barre Syndrome and the Potential Role of an Aging Immune System. Front Aging Neurosci. 2020;12:613628.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu ZD, Sun Y, Guo J, Huang YL, Qin BD, Gao Q, et al. Red blood cell distribution width and neutrophil/lymphocyte ratio are positively correlated with disease activity in primary Sjogren's syndrome. Clin Biochem. 2014;47(18):287\u0026thinsp;\u0026ndash;\u0026thinsp;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio(NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016;26(3):372-6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee YH, Song GG. Neutrophil-to-lymphocyte ratio, mean platelet volume and platelet-to-lymphocyte ratio in Behcet's disease and their correlation with disease activity: A meta-analysis.Int J Rheum Dis. 2018;21(12):2180-7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu Y, Wu Y, Cao X, Li J, Liao X, Wei J, et al. The Clinical Features and Prognosis of Anti-NMDAR Encephalitis Depends on Blood Brain Barrier Integrity. Mult Scler Relat Disord. 2021;47:102604.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie H, Zhao Y, Pan C, Zhang J, Zhou Y, Li Y, et al. Association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of first attack neuromyelitis optica spectrum disorder(NMOSD): a retrospective cohort study. BMC Neurol. 2021;21(1):389.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarnero Contentti E, Delgado-Garcia G, Criniti J, Lopez PA, Pettinicchi JP, Cristiano E, et al. An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD. Front Immunol. 2021;12:628024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFahmi RM, Ramadan BM, Salah H, Elsaid AF, Shehta N. Neutrophil-lymphocyte ratio as a marker for disability and activity in multiple sclerosis. Mult Scler Relat Disord.2021;51:102921.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharshar T, Chevret S, Bourdain F, Rapha\u0026euml;l J. Early predictors of mechanical ventilation in Guillain-Barr\u0026eacute; syndrome. Crit Care Med. 2003;31(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSutantoyo FF, Fadil, Basuki M, Fidiana, Hamdan M. Correlation Between Neutrophil-to-Lymphocyte Ratio and Motoric Deterioration in Patients With Guillain-Barre Syndrome. J Clin Neurol.2022;18(6):671\u0026thinsp;\u0026ndash;\u0026thinsp;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNing P, Yang B, Yang X, Huang H, Shen Q, Zhao Q, et al. Clinical value of C-reactive protein/albumin ratio in Guillain-Barre syndrome. Neurol Sci. 2021;42(8):3275-83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaneyala S NA, Iyer M, Gopi A. Assessment of Serum Inflammatory Markers and their Correlation with Clinical Severity and Electrophysiological Subtypes of Guillain Barre Syndrome, and Investigating their Use as Prognostic Markers of Guillain Barre Syndrome.Ann Indian Acad Neurol. 2024;27(1):101-3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabanillas-Lazo M, Quispe-Vicuna C, Cruzalegui-Bazan C, Pascual-Guevara M, Mori-Quispe N, Alva-Diaz C. The neutrophil-to-lymphocyte ratio as a prognostic biomarker in Guillain-Barre syndrome: a systematic review with meta-analysis. Front Neurol. 2023;14:1153690.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi X, Wang J, Li L, Liu L. Establishment of a single-center-based early prognostic scoring system for Guillain-Barre syndrome. BMC Neurol. 2023;23(1):97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussain J, Saqib M, Sohailkhan, Jan F, Marwat S, Khan N. Determine Serum Albumin as an Independent Biomarker for Clinical Outcome in Plasmapheresis Treated GBS Patients Pakistan Journal of Medical \u0026amp; Health Sciences. 2021;15(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShalman A, Savir S, Mechnik Steen Y, Ovanyan A, Boniel N, Koyfman L, et al. Albumin levels as a biomarker for second Intravenous Immunoglobulin (IVIG) treatment in Guillain-Barre syndrome (GBS). J Clin Neurosci. 2020;74:247-9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrelowska M, Logon K, Dziadkowiak E. Prognostic factors associated with worse outcomes in patients with GBS: A systematic review. Adv Clin Exp Med. 2025;34(3):457\u0026thinsp;\u0026ndash;\u0026thinsp;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnjum J, Rehman MAU, Nazir H, Mengal M, Dina TJ, Das D. Serum Albumin as an Independent Indicator in Guillain-Barre Syndrome Patients Undergoing Plasmapheresis. Jounal of Population Therapeutics \u0026amp; Clinical Pharmacology. 2025;32(6):1755-62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBadshah M, Shabbir G, Nabi SF, Ahmed D. Association of serum albumin levels and guillain barre syndrome (gbs) outcome. Pakistan Journal of Neurological Sciences.2018;13(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRabi R, Alsaid RM, Matar AN, Dawabsheh Y, Abu Gaber D. The role of serum albumin in critical illness, predicting poor outcomes, and exploring the therapeutic potential of albumin supplementation. Sci Prog. 2024;107(3):368504241274023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAtrash AK, de Vasconcellos K. Low albumin levels are associated with mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit. South Afr J Crit Care. 2020;36(2).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Guillain–Barré syndrome, biomarkers, prognosis, neurtrophil-to-lymphocyte ratio, albumin","lastPublishedDoi":"10.21203/rs.3.rs-8784464/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8784464/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGuillain\u0026ndash;Barr\u0026eacute; syndrome (GBS) is an acute immune-mediated polyneuropathy with a variable clinical course. Early identification of patients at risk for respiratory failure or poor functional outcomes remains challenging. This study aimed to evaluate the prognostic value of clinical features and readily available serologic biomarkers, with a particular focus on lymphocyte-based inflammatory ratios and serum albumin levels.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 126 patients diagnosed with GBS who were admitted to Chungnam National University Hospital between January 2012 and January 2022. Baseline clinical characteristics, neurological findings, and laboratory parameters\u0026mdash;including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein-to-albumin ratio (CAR), and serum albumin levels\u0026mdash;were assessed within 24 hours of admission. Serum albumin levels at two weeks after immunotherapy were collected when available. Disease severity and long-term outcomes were evaluated using the Hughes score. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify prognostic factors for respiratory failure and poor long-term outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 126 patients (mean age 54.8\u0026thinsp;\u0026plusmn;\u0026thinsp;16.3 years), 19 (15.1%) developed respiratory failure and 23 (18.2%) had poor functional outcomes at 3 months. Baseline NLR was significantly higher in patients with respiratory failure and was associated with a 1.4-fold increased risk in the unadjusted model (OR\u0026thinsp;=\u0026thinsp;1.4; 95% CI\u0026thinsp;=\u0026thinsp;1.1\u0026ndash;1.8; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). Lower baseline serum albumin levels were associated with poor long-term outcomes. Persistently low serum albumin levels at two weeks after immunotherapy were independently associated with both respiratory failure and poor long-term outcomes. ROC analysis demonstrated that serum albumin levels at two weeks showed good predictive performance for poor outcomes (AUC\u0026thinsp;=\u0026thinsp;0.818).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEarly inflammatory markers and serum albumin levels provide complementary prognostic information in patients with GBS. Elevated NLR at admission may help identify patients at risk for respiratory failure, while persistently low serum albumin levels after treatment are strongly associated with adverse long-term outcomes. These readily available biomarkers may facilitate early risk stratification and guide timely clinical management in GBS.\u003c/p\u003e","manuscriptTitle":"Prognostic Biomarkers in Guillain-Barré Syndrome: Lymphocyte-Based Ratio and Albumin Level","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-24 16:21:44","doi":"10.21203/rs.3.rs-8784464/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-11T05:38:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"168905010314910039786698963794016051345","date":"2026-05-09T12:23:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134717399661932618778787472564765086574","date":"2026-05-08T01:22:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1039373916159009012523910362067895526","date":"2026-05-07T11:04:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-19T09:59:26+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-16T21:44:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-14T00:23:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-14T00:23:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-02-04T09:05:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5bbdcd01-e55b-49a8-a3bf-1f0f9c7a693a","owner":[],"postedDate":"February 24th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-11T05:38:46+00:00","index":47,"fulltext":""},{"type":"reviewerAgreed","content":"168905010314910039786698963794016051345","date":"2026-05-09T12:23:47+00:00","index":46,"fulltext":""},{"type":"reviewerAgreed","content":"134717399661932618778787472564765086574","date":"2026-05-08T01:22:50+00:00","index":45,"fulltext":""},{"type":"reviewerAgreed","content":"1039373916159009012523910362067895526","date":"2026-05-07T11:04:04+00:00","index":39,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-24T16:21:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-24 16:21:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8784464","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8784464","identity":"rs-8784464","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}