Exploration of Medicine

Table 2. Database search results: 19 studies.

No.	Author/reference	Design	Country	Results
1	Breville et al. [6]	Review	Switzerland	Detecting patients at risk of poor outcome may improve management. Clinical poor prognostic factors: higher age, presence of diarrhea within 4 weeks of symptom onset, rapid and severe weakness progression, dysautonomia, decreased vital capacity, and facial, bulbar, and neck weakness. Biological, neurophysiological and imaging measures of unfavorable outcome: multiple anti-ganglioside antibodies elevation, increased serum and CSF neurofilaments light (NfL) and heavy chain, decreased NfL CSF/serum ratio, hypoalbuminemia, nerve conduction study with early signs of demyelination or axonal loss, and enlargement of nerve cross-sectional area on ultrasound. Depicting prognostic biomarkers aims at predicting short-term mortality and need for cardio-pulmonary support and monitoring therapeutic responses in future clinical trials.
2	Lee et al. [7]	Review	South Korea	Although ophthalmoplegia is a hallmark of anti-GQ1b antibody syndrome, recent studies have identified this antibody in patients with acute vestibular syndrome, optic neuropathy with disc swelling, and acute sensory ataxic neuropathy of atypical presentation. Ophthalmoplegia associated with anti-GQ1b antibody positivity is complete in > 50% of the patients but may be monocular or concomitant. The prognosis is mostly favorable; however, approximately 14% of patients experience relapse.
3	Vargas et al. [8]	Retrospective cohort	USA	90 patients met the inclusion criteria (45 SBRT and 45 EBRT matched cases). Balance of the covariates, SINS, age, follow-up time, and primary tumor histology after the matching process was confirmed between groups (p = 0.062, p = 0.174, and 0.991, respectively, along with matched tumor histology). The SBRT group had a higher 5-year rate of vertebral body fracture at 22.22% (n = 10) compared with 6.67% (n = 3) in the EBRT group (p = 0.044). Survival analysis was used to adjust for uneven follow-up time and showed a significant difference in fracture rates between the two groups (p = 0.044). SBRT also was associated with a higher rate of local control (86.67% vs 77.78%).
4	Inan et al. [9]	Review	Turkey	Electrophysiological studies, US, and immunological markers have been explored for discrimination; however, definitive criteria for differentiation remain elusive. Recent follow-up studies have further blurred the boundaries between recurrent GBS and A-CIDP, suggesting the persistence of underlying immune processes even in GBS patients without clinical deterioration. This emphasizes the necessity of reevaluating diagnostic criteria and treatment strategies. In conclusion, distinguishing recurrent GBS from A-CIDP remains an ongoing challenge. Existing evidence questions the categorization of recurrent GBS as a distinct entity, challenging its very existence. Continued research is necessary to refine diagnostic criteria and deepen our understanding of these conditions, ultimately advancing patient care.
5	Antoine [10]	Review	France	About 20 antibodies have been identified in immune-mediated neuropathies, recognizing membrane or intracellular proteins or glycolipids of neuron and Schwann cells. This article reviews the different methods used for their detection, what we know about their pathogenic role, how they have helped identify several disorders, and how they are essential for diagnosis. Despite sustained efforts, some immune-mediated disorders still lack identified autoantibodies, notably the classical form of GBS & CIDP. The article also tries to determine potential future developments in antibody research, particularly the use of “omic” approaches and the search for other types of biomarkers beyond diagnostic ones, e.g., those that can identify patients who will respond to a given treatment.
6	Finsterer [11]	Review	Austria	The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in 3/4 of cases, are previous infections, most commonly Campylobacter jejuni (C. jejuni), Mycoplasma pneumoniae, and cytomegalovirus. C. jejuni is responsible for about a third of GBS cases. GBS due to C. jejuni is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signaling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space.
7	Bragazzi et al. [12]	Modeling study	Iran	In 2019, there were 150,095 [95% uncertainty intervals (UI) 119,924 to 188,309] total cases of GBS worldwide, which resulted in 44,407 (95% UI 28,016 to 64,777) years lived with disability (YLDs). Globally, there was a 6.4% (95% UI 3.6 to 9.5) increase in the age-standardized prevalence of GBS per 100,000 population between 1990 and 2019. High-income Asia Pacific [1.9 (95% UI: 1.5 to 2.4)] and East Asia [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardized prevalence rates (per 100,000), respectively, in 2019. Nationally, Japan [6.4 (95% UI: 5.3 to 7.7)] and China [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardized prevalence rates (per 100,000). The age-standardized burden of GBS increased with increasing age and was higher in males in all age groups. Furthermore, the age-standardized prevalence of GBS (per 100,000) had a positive association with the level of development, as measured by socio-demographic index, although this association was not strong. Upper respiratory infections and unknown causes accounted for the highest proportions of underlying causes. Data from the Global Burden of Diseases Study (GBD) 2019 were used. GBD 2019 modelled the prevalence of GBS using hospital and claims data. YLDs were estimated as the product of the GBS prevalence and the disability weight. This article also reported proportions in the age-standardized prevalence rate that were due to 6 underlying causes of GBS.
8	Connors et al. [13]	Case report	USA	A 61-year-old male was admitted to an LTACH for the rehabilitation of GBS following COVID-19 infection and IVIG. Rehabilitation in the LTACH setting uses a variety of skilled treatment interventions to meet patient-driven goals and maximize their function to the highest level possible in preparation of their discharge to a subacute or homecare setting. In this case, this was accomplished through individual OT and PT sessions, OT/PT cotreatment sessions, and targeted group therapy sessions focused on leg, arm, and fine motor coordination exercises.
9	Galieri et al. [14]	Systematic review	Italy	A total of 32 studies met the inclusion criteria. Robotic-assisted surgery demonstrated high accuracy in pedicle screw placement (~92–94%) and reduced intraoperative blood loss and radiation exposure, although long-term clinical outcomes were comparable to conventional techniques. Intraoperative navigation improved instrumentation precision, while augmented reality enhanced ergonomic workflow and reduced surgeon distraction. AI tools showed promise in surgical planning, guidance, and outcome prediction but lacked definitive evidence of clinical superiority. Minimally invasive surgery (MIS) techniques—including endoscopic discectomy and MIS-transforaminal lumbar interbody fusion—offered reduced blood loss, shorter hospital stays, and faster recovery, with equivalent pain relief, fusion rates, and complication profiles compared to open procedures. Lateral and oblique approaches [extreme lateral interbody fusion or oblique lateral interbody fusion (OLIF)] further optimized alignment and indirect decompression, with favorable perioperative metrics. This systematic review evaluates the literature from Feb 2020 to Feb 2025 on technological and procedural innovations in lumbar spinal stenosis. Eligible studies focused on degenerative lumbar pathologies, advanced surgical technologies, and reported clinical or perioperative outcomes, including RCTs, comparative studies, meta-analyses, and large case series.
10	Palacio Giraldo et al. [15]	Systematic review	Austria	The main treatment goals for spinal metastases include local control, pain relief, improvement or prevention of neurologic symptoms, and maintenance of stability. MRI is considered the gold standard for diagnosing spinal metastases, although alternative imaging modalities are also described. Treatment options include systemic therapies, radiotherapy, and surgical techniques for metastatic lesions. The combination of SBRT with surgical spinal decompression of the spine is an evolving treatment approach with promising results. Several treatment management algorithms, including the NOMS (neurology, oncology, mechanical stability, and systemic disease), and LMNOP (localization, mechanical instability, neurology, oncology) algorithms, have been proposed to aid in the decision-making process regarding individual treatment modalities. The primary factors influencing treatment decisions are primary tumor histology and life expectancy. This review focuses on the symptoms, diagnosis & treatment of spinal metastases, which represent a late complication of the primary tumor.
11	Khan et al. [16]	Review	Bangladesh	It comprehensively examines the life-threatening nature and intensity of GBS by assessing its etiology, progression, and prevalence in low- and middle-income nations while also considering global trends. It proposed the implementation of standard efficacious treatment & diagnostic resources that are readily accessible and successful in affluent nations and should also be readily accessible in impoverished nations without any unnecessary delay. It emphasized the epidemiological data with molecular epidemiological analysis and the utilization of AI technology in low- and middle-income nations. The goal was to decrease the incidence of GBS cases and facilitate early detection.
12	Kim et al. [17]	Cohort study	Korea	The Korean National Health Insurance Service claims data from 2010 to 2016 were used to identify incident cases as newly hospitalized patients with a primary diagnosis of GBS (the 10th revision of the International Classification Disease code of G61.0). New cases were defined as patients not having claim records for GBS within one year before the hospital admission for GBS.
13	Leitner et al. [18]	Retrospective cohort study (propensity score analysis)	Austria	Single-center propensity score analyses with inverse-probability-of-treatment-weights (IPTW) of OS and short-term neurologic outcomes in MSCC patients treated with or without surgery between 2007 and 2020. Among 398 patients with MSCC, 194 (49%) underwent surgery. During a median follow-up of 5.8 years, 355 patients (89%) died. MBs was the most important predictor for spine surgery (p < 0.0001) and the strongest predictor of favorable OS (p < 0.0001). Surgery was associated with improved OS after accounting for selection bias with the IPTW method (p = 0.021) and emerged as the strongest determinant of short-term neurological improvement (p < 0.0001). Exploratory analyses delineated a subgroup of patients with an MBs of 1 point who still benefited from surgery, and surgery did not result in a higher risk of short-term oncologic disease progression. This was a single-center, open-label, RCT performed on 2 parallel groups: 50 intensive care unit adults admitted for GBS and at risk for acute respiratory failure were randomized to early mechanical ventilation via face mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, whichever occurred first).
14	Li et al. [19]	Retrospective cohort	China	This study hypothesizes that, unlike in cases of trauma and degenerative disorders, where delayed decompression surgery often leads to poor outcomes, delayed decompression surgery for malignant epidural spinal cord compression-induced paralysis yields relatively favorable results. It included patients who had been paralyzed for more than 48 hours and underwent decompressive surgery between Jan 2012 and Dec 2020. Data collected mainly included patient demographics, tumor pathologies, neurological function (Frankel grades), ambulatory status, and imaging. Primary outcome measure: neurological recovery.
15	Melone et al. [20]	RCT	France	25 patients were randomized in each group: no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000.1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events.
16	Oshomoji et al. [21]	Systematic review	Nigeria	Key findings indicate that specific autoantibodies, e.g., anti-GM1 and anti-GQ1b, are associated with distinct subtypes of GBS, contributing to its heterogeneity. Understanding these autoimmune mechanisms is crucial for improving diagnostic accuracy, therapeutic strategies, and prognostic indicators in GBS. This review highlights significant gaps in current research, emphasizing the need for further studies to explore the genetic and environmental factors that influence GBS susceptibility and the role of vaccinations in triggering autoimmune responses. It aims to elucidate the autoimmune mechanisms underlying the various subtypes of GBS, including AIDP, AMAN, acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS). A thorough literature search identified 71 studies published between 2010 and 2024.
17	Shea and Kwan [22]	Narrative review	Hong Kong, China	This review presents a comprehensive approach to the management of spinal metastases. The wide spectrum of clinical presentation in spinal metastases necessitates a personalized approach to treatment planning. This includes a comprehensive diagnostic workup, oncological management, palliation of symptoms, and surgical intervention if appropriate. A systematic and multidisciplinary approach allows optimal shared decision making to reach an evidence-informed and value-congruent treatment plan for the patient. We highlight how advances in stereotactic body radiotherapy (SBRT) and separation surgery may be incorporated into clinical management from a spine surgeon’s perspective.
18	Tewedaj et al. [23]	Retrospective cross-sectional study	Ethiopia	60 GBS patients admitted to TASH from Jan 2018 to Dec 2022. Data on demographics, clinical features, treatments, complications, and outcomes were extracted from medical records. Bivariate and multivariate logistic regression analyses identified factors associated with mortality and poor hospital outcomes. Ascending paralysis (76.7%) was the predominant presentation. Absent or reduced reflexes were seen in 91.7% of patients. The most common antecedent event was gastroenteritis (26.7%), followed by upper respiratory tract infection (URTI) (15%) and vaccination (11.7%). The mean interval from symptom onset to hospital presentation was 8.77 days, and the peak symptom severity was 4.47 days. The axonal variant (75.5%) was the most common subtype, followed by the demyelinating variant (24.5%). IVIG (intravenous immunoglobulin) was administered to 41.7% of patients. Respiratory failure requiring invasive mechanical ventilator (MV) support occurred in 26.7% of cases. The mortality rate was 10%, with mechanical ventilation being the only factor significantly associated with mortality (95% CI 2.067–184.858; P < 0.010). At discharge, 55% had a good outcome, and 45% had a poor outcome, according to the Hughes Functional Disability Scale (HFDS). MV (AOR 0.024, 95% CI 0.001–0.607) and a GBS disability score > 3 (AOR 0.106, 95% CI 0.024–0.467) were factors significantly associated with poor hospital outcomes. GBS in this cohort primarily affected individuals of young age, commonly preceded by gastroenteritis and characterized by a high frequency of the axonal variant. Mechanical ventilation was found to be significantly linked to mortality. Alongside mechanical ventilation requirements, severe disability upon presentation emerged as a crucial determinant of poor outcomes upon discharge.
19	Xu et al. [24]	Population-based study + systematic review and meta-analysis	China	A total of 1.44 billion person-years in insurance data was covered, with 3,534 GBS cases identified. The annual incidences of GBS in urban China between 2013 and 2017 ranged from 0.41 (95% CI: 0.27 to 0.58) to 0.58 (95% CI: 0.38 to 0.82) per 100,000 person-years. The incidence was the highest in Northwest China and the lowest in Northeast China. The meta-analysis included 122 articles. The quality assessment showed that the quality scores of 43.3% of studies were ≥ 0.75 (the total score is 1). The global incidence of GBS was 1.12 (95% CI: 0.98 to 1.27) per 100,000 person-years. The incidences in West Europe, South Asia, and North Europe were higher, while the incidences in Australia and New Zealand, Southeast Asia, and North Africa were lower. The incidence of enteric infections was positively associated with the incidence of GBS (coefficient = 0.0000185, P = 0.007). The incidence in Europe, Australia, and America rose significantly from 1960 to 2020 (coefficient = 0.01, t = 2.52, P = 0.015). A population-based study to calculate the incidence of GBS in urban China based on the National Urban Medical Insurance database from 2013 to 2017. To identify GBS cases, natural language processing was used first for handling the lengthy and unstructured diagnostic information and then checked by prestigious neurologists. Secondly, a systematic review and meta-analysis were performed to analyze the incidence of GBS worldwide. Up to July 4, 2022, Medline, Embase, and Web of Science were retrieved to identify the population-based studies regarding the incidence of GBS. The basic information and the statistics regarding incidence were extracted. Quality assessment considered sample representativeness, condition assessment, and statistical methods.

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A-CIDP: acute onset chronic inflammatory demyelinating polyneuropathy; AI: artificial intelligence; CSF: cerebrospinal fluid; EBRT: external beam radiation therapy; GBS: Guillain-Barré syndrome; GM1: ganglioside M1; GQ1b: ganglioside Q1b; LTACH: long-term acute care hospital; MBs: modified Bauer score (likely a spinal metastasis grading scale variant); MRI: magnetic resonance imaging; MSCC: malignant spinal cord compression; TASH: Tikur Anbessa Specialized Hospital (Ethiopia’s main tertiary hospital in Addis Ababa); OS: overall survival; OT/PT: occupational therapy/physiotherapy; RCTs: randomized controlled trials; SINS: Spinal Instability Neoplastic Score; US: ultrasonography.

Declarations

Author contributions

OA: Conceptualization, Investigation, Formal analysis, Writing—original draft, Data curation, Writing—review & editing. M Subih: Conceptualization, Investigation, Formal analysis, Writing—original draft, Data curation, Writing—review & editing. LS: Conceptualization, Investigation, Formal analysis, Writing—original draft. M Stublla: Conceptualization, Investigation, Formal analysis, Writing—original draft, Data curation, Writing—review & editing. DB: Writing—review & editing. PT: Conceptualization, Investigation, Formal analysis, Writing—original draft, Data curation, Writing—review & editing. OS: Writing—review & editing. AEEAE: Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Patricia Tai, who is the Editorial Board Member and Guest Editor of Exploration of Medicine, and Omar Alqaisi, who is the Guest Editor of Exploration of Medicine, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

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Not applicable.

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All relevant data is contained within the manuscript.

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