Two case scenarios to illustrate principles of management

A 75-year-old nursing home resident in Canada with pre-existing diffuse metastatic prostate cancer was diagnosed with suspected SCC at 9 am on a Friday in 2023. The on-call neurosurgeon was paged at 10 am but never responded, despite several attempts. Later, the doctor from the rural hospital called the cancer center; somehow, the on-duty radiation oncologist was tied up in a meeting. A busy clerk took the call instead and did not inform the oncologist promptly. The message on a piece of paper was noticed only around 4 pm. The radiation oncologist returned the call and requested the local doctor to administer intravenous dexamethasone 4 mg immediately and also arranged an ambulance to transfer the patient to the cancer center. It took about seven hours to reach the emergency room from the hospital due to inadequate ambulance staff. The radiation oncologist contacted his on-call team of physicists and radiation therapists to provide emergency radiotherapy since the patient was inoperable due to comorbidities and paraplegia likely lasted more than 24 h, which historically benefited less from surgery. He also started subcutaneous degarelix (a gonadotropin antagonist), 240 mg, which is preferred because it does not cause a gonadotropin-releasing hormone flare and reduces prostate-specific antigen and testosterone levels on the same day. The patient suffered from significant complications from his SCC, leading to higher nursing costs over the next four months before his eventual death, such as turning him in bed. The patient became depressed due to his disability and felt like a financial burden to his beloved adult children, as most Canadians do not have substantial savings.

A 40-year-old woman came to the emergency room in London, Ontario, with sudden paraplegia that developed over three days. She had always been healthy and had no family history of cancer. The only relevant history was that she experienced diarrhea two weeks earlier. The emergency room doctor considered the differential diagnoses of GBS vs. SCC. The radiation oncology team was consulted, and an MRI scan was ordered. The MRI results were normal. A lumbar puncture showed albuminocytological dissociation, with elevated cerebrospinal fluid (CSF) protein levels but no pleocytosis. Nerve conduction studies confirmed the GBS diagnosis, likely secondary to Campylobacter jejuni infection. She was treated with IVIG and gradually recovered over three weeks with physiotherapy.

The importance of timely multidisciplinary communication and prompt intervention in both GBS and SCC is emphasized by these cases. Delays can lead to irreversible neurological deficits, especially in SCC. The GBS case illustrates why autoimmune neuropathies should be considered when diagnosing acute paralysis, particularly following infectious prodrome to facilitate early immunotherapy.

Study design

This study utilized a scoping review methodology guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) to map the existing literature, clarify key concepts, and identify gaps in research regarding the emergency differentiation of GBS and SCC, particularly given the heterogeneous nature of the available evidence [5]. Prospective registration of the protocol is not required.

Search strategy

The scoping review was conducted to address the complexity of differentiating acute paraplegia in emergency settings, a topic for which recent advances require synthesis. The review aims to provide an overview of existing studies and map the evidence landscape. The PRISMA-ScR methodology was used to ensure transparency and rigor. The literature search was conducted across Scopus, PubMed, MEDLINE, ScienceDirect, and CINAHL databases, covering the period from January 2020 to June 2025. The search was limited to this timeframe to capture the most recent evidence, contemporary diagnostic approaches, and current multidisciplinary management strategies relevant to emergency care. Earlier landmark studies were cited selectively where necessary to provide historical context.

Search terms included ‘Guillain-Barré Syndrome’, ‘autoimmune neuropathy’, ‘molecular mimicry’, and ‘spinal cord compression’, combined with Boolean operators. Two independent reviewers screened titles and abstracts for relevance, followed by full-text evaluation. Inclusion criteria encompassed English-language clinical studies, case reports, and reviews focused on epidemiology, pathophysiology, diagnostics, and management. Discrepancies in selection were resolved through consensus. A PRISMA-ScR flow diagram (Figure 2) illustrates the selection process. Database searches yielded an initial total of 3,420 records. After eliminating 720 duplicate records, 2,700 unique records were screened for titles and abstracts; 2,480 were excluded based on predefined criteria and lack of relevance. Two hundred and twenty full-text articles were then evaluated for eligibility. Two hundred and one of these were excluded for various reasons, including non-empirical study designs (n = 60), non-English language (n = 30), non-relevant populations (n = 71), and pediatric populations (n = 40). Ultimately, 19 studies met the inclusion criteria and were incorporated into the review.

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Figure 2. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) flow diagram. Adapted from “The PRISMA 2020 statement: an updated guideline for reporting systematic reviews” by Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. BMJ. 2021;372:n71 (https://doi.org/10.1136/bmj.n71). © 2021 The Author(s). CC BY 4.0.

Data analysis

Given the scoping nature of this review and the diversity of the 19 included studies (ranging from case reports to retrospective cohorts), a narrative synthesis approach was employed. Quality assessment was not performed, consistent with standard scoping review methodology, as the primary aim was to map the breadth of available evidence and identify research gaps rather than to assess the efficacy of interventions. While a formal quality assessment, such as Mixed Methods Appraisal Tool (MMAT) or Risk of Bias In Systematic reviews (ROBIS), is typically reserved for systematic reviews, this scoping review evaluated sources’ credibility based on study design rigor and peer-review status.

Thematic analysis

Five main areas of clinical management were identified through thematic analysis using iterative coding cycles. The data was collected and analyzed using a thematic approach. The studies were categorized based on key themes: etiology, clinical manifestations, diagnostic methods, therapeutic interventions, and prognosis. Qualitative thematic coding was performed manually by the authors. Dedicated qualitative data analysis software (such as NVivo or ATLAS.ti) was not used, as the scope and number of included studies allowed for structured manual coding. This enabled a thorough comparison of the conditions and facilitated the identification of parallels and differences pertinent to acute paraplegia presentations. Thematic synthesis was used to integrate data from multiple studies to draw insightful conclusions about clinical management and outcomes.

SCC

Recurring delays and missed diagnoses of SCC have been consistently reported in clinical practice, highlighting the need for an updated review of current management strategies. SCC, especially malignant epidural SCC (MESCC), happens when metastatic tumors invade the vertebral column and press on the spinal cord. This can cause pain, motor problems, and paralysis. Quick action is essential to protect neurological function and improve quality of life. Recent surgical studies highlight the changing role of decompressed surgery in MESCC treatment as follows.

Surgery

Radiotherapy

Artificial intelligence (AI) is increasingly used in radiotherapy treatment planning, dose optimization, and dosimetry [26]. Other areas of radiotherapy advances include the following.

Combining surgery and radiotherapy

The combination treatment offers synergistic benefits. Radiotherapy is most effective when administered within 24 h of diagnosis. Postoperative radiotherapy enhances tumor control and reduces the risk of recurrence [33]. In terms of patient selection, prognostic tools like the modified Bauer score and Tokuhashi score help identify candidates who will benefit most from surgery and/or radiotherapy diagnosis [34, 35]. The Tokuhashi score, developed initially and later revised by Tokuhashi et al. [36], is a validated prognostic scoring system designed to estimate survival and guide treatment decisions in patients with spinal metastases. In clinical practice, the Tokuhashi score is widely used to guide treatment decisions by estimating survival and identifying patients who may benefit from surgery, radiotherapy, or conservative treatment (Tables 4 and 5). Unnecessary aggressive treatment will tire out the patient and caregiver, as well as wasting scarce healthcare resources. A multidisciplinary approach can achieve optimal outcomes, but it requires significant effort and collaboration among neurosurgeons, radiation oncologists, and palliative care teams. Personalized treatment plans based on tumor type, neurological status, and life expectancy are essential [15, 22]. Both papers discuss modern strategies for spinal metastases, highlighting the role of multidisciplinary, personalized approaches based on clinical and oncologic parameters, as well as the estimation of survival.

Future directions for SCC

Digital implants and neurostimulation, with experimental technologies like brain-spine interface implants and stem cell research, can restore mobility in spinal cord injury patients [37]. Use of AI in image analysis, real-world data from retrospective analyses from academic centers are helping refine treatment protocols and identify gaps in care [26, 38].

GBS

GBS is less well-known. It is an acute autoimmune demyelinating polyneuropathy [13]. It is a severe inflammatory polyneuropathy with a clinically rapid onset of muscle weakness and sensory disturbances due to immune-mediated damage of the peripheral nervous system [12]. The global incidence of GBS ranges from 0.89 to 1.89 cases per 100,000 population per year, with regional variations. The incidence in 2019 was approximately 150,095 cases worldwide, or 1.9 per 100,000 age-standardized point prevalence [16]. The incidence is higher among individuals over 50 years of age than among those under 50, increasing from 1.7 per 100,000 in those under 50 to 3.3 per 100,000 in those 50 or older. The relative risk is 1.78 for men and is affected more frequently than among women [12]. Prevalence data for GBS are shown in Table 6 [39–41]. Sejvar et al. [40] reported a comprehensive meta-analysis that remains one of the most cited sources for global and regional GBS incidence rates. Xu et al. [24] reported the most recent data in 2024.

Given its potential for morbidity, especially respiratory failure and long-term disability, understanding GBS is essential for all healthcare workers. Early recognition and intervention are crucial because approximately 25% of patients will need mechanical ventilation due to respiratory muscle weakness [20]. The authors also pointed out that the death rate in GBS ranges from 3% to 7%. This indicates that while many patients recover, some may experience persistent neurological deficits or fatigue that impact their quality of life. Furthermore, GBS places a considerable economic burden. The direct medical costs per patient can be high in high-income countries, covering expenses for hospitalization, intensive care, and rehabilitation services. Indirect costs, like lost productivity due to disability and long-term disability, also contribute to the overall economic impact.

In summary, GBS is a rare but serious neurological disorder that occurs globally. The incidence depends on region, age, and sex. It constitutes a serious health and economic challenge. Recent national data from South Korea also highlighted that GBS imposes a considerable economic and healthcare burden, emphasizing the need for improved surveillance and management strategies [17]. This publication presents a comprehensive analysis of GBS burden across 204 countries, highlighting disparities in incidence and data availability, especially in low-resource regions. Another publication also explores differences in GBS presentation and outcomes across regions, emphasizing the need for improved surveillance and diagnostic infrastructure in underrepresented areas [17].

The financial impact of Campylobacter infections in the USA is significant, with costs associated with GBS estimated at $1.7 billion each year [42]. Most of this cost stems from indirect factors like premature death, while direct medical expenses account for approximately $0.2 billion. When factoring in Campylobacter-associated GBS and its related costs, the total economic burden may reach $8 billion annually. This highlights the urgent need to address the public health implications of Campylobacter infections and their connection to GBS to mitigate these substantial financial strains.

Important considerations in GBS involve differential diagnoses that also present with acute weakness. SCC requires immediate intervention with corticosteroids, surgical decompression, and/or radiotherapy. Other urgent differentials include stroke, acute encephalitis, botulism, and toxin exposure—each necessitating specific emergency treatments, as delays can lead to irreversible neurological damage. Another important consideration is the public concern over vaccination, which stems from the rare association of GBS with certain vaccines [43, 44], such as those for influenza [45] and coronavirus disease 2019 (COVID-19) [46, 47]. However, a 2022 study supports the long-term immunological safety of multiple vaccinations, showing no evidence of autoimmune or lymphoproliferative complications over a 5-year follow-up [48].

Another notable point is the limited specific epidemiological data on GBS. Nevertheless, a notable outbreak in early January 1976 occurred in Salt, Jordan, following contamination of the water supply, resulting in gastroenteritis. This study involved 19 cases of GBS, suggesting a possible localized increase in incidence due to environmental factors [46].

Pathophysiology of GBS

GBS is an acute autoimmune neuropathy in which the immune system mistakenly attacks parts of the peripheral nervous system, leading to muscle weakness and often paralysis [49]. Because of the complexity and variety of the underlying pathophysiological mechanisms, GBS involves both humoral and cellular immune responses. Vaccines can rarely be linked to GBS. The pathogenesis of GBS also involves cellular mechanisms in addition to humoral mechanisms. Within peripheral nerves, inflammation and demyelination occur because of infiltration of activated T lymphocytes and macrophages. The characteristic muscle weakness results from this infiltration, leading to demyelination and axonal degeneration that disrupts nerve conduction. Molecular mimicry is a well-described principal mechanism by which GBS is induced. In this instance, structural similarities between microbial antigens and components of host nerve tissue trigger an autoreactive immune response. In the context of GBS, infections with pathogens such as Campylobacter jejuni can induce the production of antibodies that cross-react with gangliosides. These sialic acid-containing glycosphingolipids are highly expressed in the peripheral nervous system. The immune-mediated damage to nerve tissues is due to this cross-reactivity. GBS is the most commonly unrecognized sequela of Campylobacter jejuni infection. The bacterium’s lipo-oligosaccharides (LOS) exhibit molecular mimicry with human gangliosides ganglioside M1 (GM1) and ganglioside D1a (GD1a). This mimicry triggers the production of antiganglioside antibodies, which bind to nerve tissues and activate complement pathways, resulting in nerve damage [49].

Test results in specific GBS subtypes show the presence of antiganglioside antibodies. These antibodies result in complement activation and subsequent injury of the nerve via the target of specific gangliosides present on neuronal membranes [11]. In particular, anti-GM1 antibodies are common in the acute motor axonal neuropathy (AMAN) variant of GBS, and anti-ganglioside Q1b (GQ1b) antibodies in the Miller Fisher syndrome variant, which manifests as ophthalmoplegia, ataxia, and areflexia [7, 11].

GBS is a spectrum of pathological subtypes, mainly distinguished by the degree of nerve injury from relatively benign to severe weakness and respiratory distress [50]. The acute inflammatory demyelinating polyneuropathy (AIDP) subtype is an immune-mediated demyelination wherein the peripheral nerve myelin sheath is damaged, thus causing slow motor nerve conduction velocities. However, the AMAN subtype is defined by direct degeneration of the axons without prominent demyelination, but with frequent anti-GM1 antibodies and preceding Campylobacter jejuni infections [51]. Antiganglioside antibody binding to neuronal membranes starts a cascade of reactions resulting in membrane attack complex (MAC) formation [10]. For its part, the MAC disrupts the neuronal membrane integrity and causes cellular damage with subsequent clinical manifestations of GBS [10, 21]. Recent studies have demonstrated how gut dysbiosis and increased intestinal permeability influence immune responses in GBS, opening up new possibilities for microbiome-targeted therapeutic interventions and diagnostic biomarkers. More research is required to confirm these associations. Comprehending these intricate relationships holds potential for personalized medicine strategies in autoimmune neuropathies [10].

The demyelination process impairs nerve signal transmission—a key pathophysiological hallmark of GBS. Early, common symptoms, such as limb weakness and difficulties with swallowing and breathing emphasizes the importance of early detection and treatment. This highlights the severity of untreated GBS, which can progress to flaccid paralysis [6]. The hallmark of GBS is progressive, symmetric, symptomatic muscle weakness, beginning in the legs and progressing proximally [6]. Patients frequently complain of paresthesia and numbness preceding or accompanying the weakness [52]. The most common cranial nerve involvement includes facial weakness and also bulbar symptoms of dysphagia and dysarthria [52]. In some instances, autonomic dysfunction can occur as fluctuations in blood pressure, cardiac arrhythmias, and failure of sphincters [53]. In severe cases, respiratory muscle weakness necessitates ventilatory support [20, 23].

Genetic susceptibility and environmental factors for GBS

Since not all GBS patients have antecedent infections, and the definition of molecular mimicry for autoimmune disease is controversial, additional contributory factors are involved. There may be a genetic predisposition associated with increased susceptibility, and some human leukocyte antigen (HLA) types may predispose a person to increased risk. Although the onset of this disease is unpredictable, it may also be influenced by environmental factors, such as the strain of the infecting pathogen or the host’s immune status [48].

Causal/risk factors of GBS

GBS is primarily driven by immune dysregulation following infections. From a functional perspective, several underlying triggers may contribute to this immune dysfunction, including gut dysbiosis and increased intestinal permeability, chronic viral persistence, heavy metal or environmental toxin exposure, stress-induced cortisol imbalance, nutrient deficiencies (e.g., vitamin D, B12, omega-3s), and, in rare cases, vaccinations [11, 54]. These factors collectively disrupt immune tolerance and regulatory pathways, increasing the risk of autoimmune reactions targeting the nervous system [55, 56]. Identifying and addressing these root causes through targeted diagnostics and integrative therapies can support immune balance and neurological recovery [57].

In the two weeks preceding GBS, the virus usually causes an infectious illness [11, 53]. The most commonly documented antecedent is Campylobacter jejuni infection, but cytomegalovirus, Epstein-Barr virus, influenza, and Mycoplasma pneumoniae have also been reported [11, 53]. Recent studies have begun to explore a potential association with SARS-CoV-2 infection; however, insufficient evidence exists to clarify the mechanisms by which these diseases may be causally linked. Other risk factors, aside from recent vaccination or surgical procedures, are scarce [11, 58].

Diagnostic tests

Specific investigations support the diagnosis of GBS, which is primarily clinical. Albuminocytological dissociation is often identified through lumbar puncture, characterized by elevated CSF protein levels without pleocytosis [58, 59]. Nerve conduction studies help confirm the diagnosis and distinguish subtypes [58, 59]. Other potential causes of acute flaccid paralysis can be ruled out with MRI [6].

Although nerve conduction studies and lumbar puncture with albuminocytologic dissociation are the gold standards for diagnosing GBS, early testing can yield false-negative results, requiring repeat evaluations. Although MRI requires substantial resources and may not always be available, it is essential for ruling out SCC and other mimics. To prevent misdiagnosis, clinicians should integrate clinical findings with diagnostic tests and consider alternative diagnoses early in the presentation, such as SCC when interpreting MRI images [58–60].

Complications

GBS is often self-limiting with appropriate treatment, but it may lead to serious neurological, respiratory, autonomic, and psychological complications, particularly in severe or untreated cases. In approximately a quarter of the patients, severe complications occur, including respiratory failure due to diaphragmatic weakness, which may require mechanical ventilation [33]. Consequently, autonomic dysfunction may lead to life-threatening cases of cardiac arrhythmias and blood pressure instability [60]. Another risk of prolonged immobility is deep vein thrombosis and pulmonary embolism. However, chronic pain and fatigue can last and negatively impact long-term quality of life [58].

Neuromuscular complications include persistent weakness or paralysis, and many patients experience chronic neuropathic pain [58]. Additional issues such as bladder dysfunction and significant psychological distress, including anxiety, depression, or post-traumatic stress, may occur [58]. Furthermore, about 5–10% of patients may progress to chronic inflammatory demyelinating polyneuropathy (CIDP), necessitating long-term immunotherapy [9]. Early recognition and management of these complications are essential to optimize outcomes and prevent long-term disability (Table 7).

Medical and nursing management of GBS

Early immunomodulatory therapy with IVIG or plasmapheresis is crucial for reducing disease severity and improving outcomes [61, 62] (Table 8). In Table 8, * indicates supportive care, which is the main responsibility of the nurses and includes continuous monitoring of respiratory function with early intervention for respiratory failure, managing autonomic dysfunction, and preventing deep vein thrombosis caused by physical inactivity [63, 64]. Other nursing interventions involve maintaining the airway, ensuring proper nutrition, and preventing pressure ulcers. Both nurses and doctors should provide psychological support to patients and families during the recovery process [59]. Therefore, this table highlights the specialized services offered only by nurses. Nurses are in a privileged position to help patients and their families go through this healing journey.

Limitations

The limitation of this review to English-language studies and the potential for publication bias are its main limitations. The variety of study designs, the small sample sizes in case reports, and the absence of randomized trials in some fields hamper evidence synthesis. Notably, there is a dearth of high-quality information regarding the effects of novel therapies on quality of life and long-term rehabilitation outcomes. To close these gaps, longitudinal and interventional studies should be given top priority in future research. A key finding of this scoping review is the paucity of literature directly addressing the emergency differentiation between GBS and SCC. Only 19 studies met the inclusion criteria, suggesting that while these conditions are well-studied individually, there is a lack of integrated research focusing on their simultaneous consideration in acute care settings. This highlights the urgent need for future prospective studies to develop unified diagnostic protocols for acute paraplegia in the emergency department.

Future research directions

These include evaluating minimally invasive surgical techniques in SCC, optimizing immunotherapy protocols, investigating integrative treatment approaches, and validating early diagnostic biomarkers for GBS. It’s also crucial to conduct extensive epidemiological research to inform clinical recommendations tailored to a given area.