Guillain-Barre Syndrome

Etiology

The etiology of GBS includes infectious, immune-mediated, and noninfectious triggers:

Infections

• The most common antecedent event.
• The most common causative pathogens at the time of seroconversion are Campylobacter jejuni, hepatitis E virus, cytomegalovirus, Mycoplasma pneumoniae, Epstein-Barr virus, and HIV.[2][3] Haemophilus influenzae and varicella-zoster virus have also been associated with GBS.[4][5]
• Arboviruses, such as the Zika virus, dengue virus, chikungunya virus, and Japanese encephalitis virus, are also commonly implicated in GBS.[6][7][8][9][10]
• The causal association between the COVID-19 virus and GBS remains controversial.[11][12] 

Vaccines

• There may be an elevated risk of GBS with the COVID-19 adenovirus vector vaccine Ad26.COV2.S (Janssen/Johnson and Johnson COVID-19 vaccine) and ChAdOx1 (chimpanzee adenovirus Oxford 1), but not with the messenger ribonucleic acid (mRNA) vaccines BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna).[13][14][15][14]
• Influenza vaccines are associated with an increased risk of GBS.[15] The 1976 swine influenza (A/New Jersey) vaccine was associated with the highest risk of GBS, with relative risks ranging from 4 to 7.6.[16]
• The risk of GBS after vaccination with the human papillomavirus vaccine, the hepatitis B vaccine, and the recombinant zoster vaccine has been widely debated.
• Quadrivalent meningococcal diphtheria toxoid conjugate vaccine may pose a minimal increased risk of GBS.[17]

Despite the above risks, the current consensus is that the benefits of vaccination outweigh the risks of GBS. 

Noninfectious

Potential noninfectious triggers include the following:

• Surgical procedures
• Autoimmune disorders (eg, systemic lupus erythematosus)
• Trauma
• Medications (eg, immune checkpoint inhibitors/tumor necrosis factor-α inhibitors/type I interferons)
• Malignant neoplasm (eg, lymphoma)

Epidemiology

The estimated global annual incidence of GBS ranges from 1.1 to 1.8 per 100,000 person-years. The incidence in children (0-15 years) ranges from 0.34 to 1.34 per 100,000 person-years.[18] The incidence is variable globally, with rates ranging from 0.84 to 1.91 per 100,000 person-years in Europe and North America, and from 0.40 per 100,000 person-years in Brazil to 2.5 per 100,000 person-years in Curaçao and Bangladesh.[18][19][20][21][22] Approximately 70% of GBS cases are preceded by infections.[18] Men are affected more often than women, with a ratio of approximately 1.5:1.[23][24][25]

Pathophysiology

Neural Targets and Molecular Mimicry

The neural antigens targeted by GBS vary with disease phenotype. The axonal variants of GBS most commonly target gangliosides. Gangliosides are sialic-acid–containing glycosphingolipids that are present in peripheral nerve fibers. Gangliosides facilitate cell-cell interactions between neurons and glia, modulate receptors, and regulate growth. The phenotypic expression of GBS often depends on the anatomic distribution of the gangliosides to which the antiglycolipid antibodies bind, as well as the binding specificity of these antibodies.[26][27] 

The lipooligosaccharides of Campylobacter jejuni, the most common antecedent infection in GBS, contain ganglioside-like moieties. Molecular mimicry in the production of antiganglioside antibodies is well established in acute motor axonal neuropathy and the Miller-Fisher variant, as evidenced by multiple observations. In the ganglioside nomenclature (eg, GM1b), G stands for the ganglioside, and the second letter denotes the number of sialic acid residues (eg, M= 1, D= 2, T= 3, Q= 4). The numerical value indicates the number of neutral carbohydrates, and the lowercase letter depicts the isomeric position of the sialic acid residue. Antiganglioside antibodies are complement-fixing immunoglobulin G (IgG) isotypes, primarily IgG1 and IgG3.  

The binding targets of antibodies and the role of molecular mimicry in acute inflammatory demyelinating polyradiculoneuropathy (AIDP) remain largely unknown. In the case of immune crossreactivity associated with Mycoplasma pneumoniae, antigens cross-react with galactocerebroside (GalC). GalC is a glycolipid enriched in the Scells' cells’ myelin sheath. GalC, along with sialosynlneolactotestrasylceramide (LM1, another myelin glycolipid), and moesin (an antigen located on Schwann cell microvilli at nodes), have also been implicated in cytomegalovirus-associated AIDP. 

Pathogenesis

In the classic example of GBS triggered by C jejuni, the pathogen's ganglioside lipooligosaccharides are first recognized by antigen-presenting cells. These cells trigger autoreactive T cells, which release multiple cytokines and promote B-cell–mediated antibody production against myelin glycolipids. Cytokines upregulate adhesion molecules on endothelial cells, facilitating the breakdown of the blood-nerve barrier and permitting activated T cells, antimyelin antibodies, and macrophages to cross. 

Within the peripheral nervous system, these autoreactive T cells differentiate into T helper 1, T helper 2, or T helper 17 cells. T helper 1 cells facilitate macrophage recognition of Schwann cells by producing tumor necrosis factor-α and interferon-γ. Activated macrophages directly damage Schwann cells and axons, leading to demyelination and secondary axonal degeneration through the production of proinflammatory cytokines, proteases, and reactive oxygen species. T helper 2 cells promote B-cell differentiation into antiganglioside-producing plasma cells through the action of interleukins.[28]

Antiganglioside antibodies produced by local B cells or those that cross the injured blood-nerve barrier further contribute to nerve damage by activating complement (C3b receptor-mediated phagocytosis and membrane attack complex [MAC] formation) or by binding to Fcγ receptors on macrophages. The latter further activates macrophages, thereby sustaining inflammation and leading to additional neural injury.[29] In addition, downregulation of autoregulatory T cells impairs tolerance and suppresses other immune cells (B cells, T cells, or dendritic cells), further contributing to the immunologic destruction of nerves. In summary, the common pathway of inflammatory nerve damage in GBS involves activation of the classical complement pathway, Fcγ receptors, and the macrophage-microglial system. 

Pathophysiologic Differences of Subtypes

There are several pathophysiologic differences between the 2 most common electrophysiologic subtypes of GBS.

Acute motor axonal neuropathy variant:

• Ganglioside antigens target nodal structures, ventral roots, and nerve terminals via complement activation and formation of the MAC.
• Complement-mediated attack leads to loss of voltage-gated sodium channels and paranodal myelin detachment, resulting in a reversible conduction block that resolves with prompt treatment.
• During intense immune responses, axonal degeneration results from intra-axonal calcium accumulation, mediated by mechanisms such as inhibition of the sodium-potassium pump and MAC-mediated axolemmal perforation.[30]

Acute inflammatory demyelinating polyneuropathy variant:

• MAC formation leads to myelin vesicular degeneration.
• Macrophages subsequently scavenge the myelin debris.
• Schwann cells later give rise to progeny that surround demyelinated nerve fibers to regenerate myelin.
• Offspring Schwann cells produce short internodes by encasing short portions within the existing internode.
• Intense inflammation can lead to secondary axonal loss.[31] 

History and Physical

Clinical Features

GBS can present with a wide spectrum of subtypes and is often classified based on the electrophysiologic characteristics (axonal versus demyelinating forms). The classic sensorimotor GBS manifests approximately 10 days after the antecedent event. The initial symptoms include lower back pain from nerve root inflammation and distal paresthesias (acroparesthesias). The characteristic symmetric weakness involving proximal and distal muscles results from involvement of both proximal nerve roots and distal nerves (polyradiculoneuropathy), where the blood-nerve barrier is weakest.

An ascending pattern of weakness is more common, with the lower extremities affected earlier than the upper extremities. Deep tendon reflexes are typically absent (areflexia) or reduced (hyporeflexia), but patients with the acute motor axonal neuropathy (AMAN) or Bickerstaff variants may have preserved reflexes or hyperreflexia.[32] In addition to extremity weakness, cranial nerve–innervated muscles, particularly those of the face, oropharynx, and extraocular muscles, may also be involved. Facial muscles are most frequently affected, followed by oropharyngeal and then extraocular involvement.

Most GBS symptoms follow a monophasic course, with recurrence in fewer than 5% of patients. Approximately 10% of patients experience treatment-related fluctuations, defined as up to 2 relapses within 8 weeks of treatment initiation, characterized by worsening of at least 1 grade on the GBS disability scale or a decrease in the Medical Research Council (MRC) sum score. Such treatment-related fluctuations typically respond to reinitiation of previously administered immunomodulatory therapy. 

In a subgroup of patients who experience 3 or more relapses or symptom progression beyond 8 weeks, the diagnosis of acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) should be considered. An intermediate subtype between GBS and CIDP that reaches its nadir between 4 and 8 weeks is termed subacute inflammatory demyelinating polyradiculoneuropathy. Such cases should be closely monitored because they are at risk of future relapses and progression to CIDP. Autonomic abnormalities occur in approximately two-thirds of cases with variable severity. The autonomic manifestations include cardiac arrhythmias (most commonly sinus tachycardia), labile blood pressure, orthostatic hypotension, abnormal sweating, gastrointestinal dysmotility (eg, paralytic ileus), pupillary abnormalities, and genitourinary dysfunction (eg, urinary retention).[33]

GBS Subtypes 

Acute inflammatory demyelinating polyneuropathy 

• Antigenic targets: Galactrocerebroside, LM1, and moesin.

Acute motor axonal neuropathy 

• Clinical features: More severe disease (eg, greater weakness at nadir, delayed recovery of independent ambulation). Deep tendon reflexes may be preserved or hyperreflexic.
• Antibodies to monosialotetrahexosylganglioside 1 (GM1) and disialoganglioside 1a (GD1a) (expressed on the axolemma of intramuscular motor nerve axons at the node of Ranvier) are primarily implicated.
• Other associated antibodies are GM2, GD1b, GM3, GD1a, GD1b, GT1b, and N-acetylgalactosaminyl GD1a.

Acute motor-sensory axonal neuropathy 

• Clinical features: More severe disease with frequent autonomic and cranial nerve dysfunction.
• Associated with anti-GM1 and anti-GD1a antibodies.[5]

Facial diplegia (bifacial weakness with paresthesias)

• Acute bilateral facial weakness reaches a nadir within 4 weeks. 
• Distal limb paresthesias in hands and feet.
• Diminished or absent deep tendon reflexes.
• Absence of limb weakness, ataxia, or other cranial nerve involvement.
• Antiganglioside antibodies are usually absent; anti-GM2 may be associated with cytomegalovirus infection.[34]

Miller Fisher syndrome 

• Clinical triad of ophthalmoplegia, ataxia, and areflexia in complete forms.
• Antibodies to GQ1b (which is strongly expressed in the reticular formation, extraocular muscles, and muscle spindles) are found in 85% to 90% of patients.

Bickerstaff brainstem encephalitis 

• Miller Fisher syndrome–related disorder.
• Clinical features: Impaired consciousness plus Miller Fisher syndrome features (ophthalmoplegia, ataxia, and areflexia), or paradoxical hyperreflexia.
• Associated with GQ1b and GT1a antibodies.

Pharyngeal-cervical-brachial variant

• Clinical features: Dysphagia.
• Associated with antibodies to GT1a (strongly expressed in the glossopharyngeal and vagus nerves). GQ1b and GD1a have also been reported.[5]

Sensory ataxia variant

• Profound ataxia of peripheral origin due to proprioceptive loss.
• Areflexia or hyporeflexia.
• Absence of muscle weakness and no ophthalmoplegias.
• Anti-GQ1b IgG or anti-GT1a antibodies may be present and bind to the neurons of the spinocerebellar tract.[35]

Paraparetic

• Weakness is restricted to the lower extremities without involvement of the upper extremities. Some patients exhibit reduced or absent upper-extremity reflexes or paresthesias.
• Mild disease activity and excellent prognosis.
• Anti-GM1 IgG antibodies may be present.[36]

Acute sensory neuropathy/pure sensory ataxic variant/sensory GBS

• Acute onset of sensory symptoms without muscle weakness.
• Numbness and paresthesias peak within 4 weeks, with sensory loss of pain, temperature, and proprioception. 
• Absent diminished reflexes but no muscle weakness.[37]

Acute small fiber neuropathy

• Burning dysethesias and numbness with loss of pain and temperature sensation.
• Proprioception, vibration, and muscle strength are intact.
• Normal or brisk deep tendon reflexes.[38]

Acute autonomic neuropathy/acute pandysautonomia

• Acute onset of autonomic dysfunction affecting the parasympathetic and sympathetic nervous systems.
• Orthostatic hypotension, anhidrosis, gastrointestinal dysfunction (constipation and ileus), bladder atony, impotence, pupillary abnormalities, and mild sensorimotor features may be present.[39]

Evaluation

The diagnosis of GBS is primarily based on clinical history and neurologic examination. Ancillary investigations such as cerebrospinal fluid (CSF) analysis and electrodiagnostic studies can support the diagnosis and help exclude mimics. The Brighton criteria outline 4 levels of diagnostic certainty (see Table. Diagnostic Criteria for Guillain-Barré Syndrome). Key diagnostic features include clinical presentation, CSF findings, nerve conduction studies, and disease course. However, the diagnostic criteria have limitations and may miss variants of GBS.[4]

Table. Diagnostic Criteria for Guillain-Barré Syndrome 

CSF, cerebral spinal fluid; GBS, Guillain-Barré syndrome

Diagnostic features adapted from the National Institute of Neurological Disorders and Stroke.

Laboratory Investigations

The following laboratory tests help rule out other potential causes:

• Complete blood cell count
• Comprehensive metabolic profile with magnesium and phosphate levels
  • Hypermagnesemia and hypophosphatemia may also present with acute weakness.
• Thiamine level
  • Low thiamine levels or dry beriberi can mimic GBS.
• Glycosylated hemoglobin
• Thyroid function testing
• Toxicology testing, if indicated
  • Abdominal pain, garlic breath, Mee lines, and hair thinning may indicate arsenic exposure.
• Paraneoplastic panel
  • Especially in Hodgkin and non-Hodgkin lymphoma

Antiganglioside antibody testing is not recommended for routine use due to its limited diagnostic value and assay variability.[41] An exception is the anti-GQ1b antibody, which is found in up to 90% of patients with Miller Fisher syndrome.

CSF Analysis

The CSF analysis can support the diagnosis of GBS and exclude other etiologies. Albuminocytologic dissociation, with elevated total protein but normal cell count, is the most typical CSF finding in GBS. This finding is due to increased blood-nerve barrier permeability at the level of proximal nerve roots. Protein levels may be within the reference range in approximately half of patients during the first week of illness, but increase in 70% to 90% of patients by the end of the second week.[42][43]

Mild CSF pleocytosis (10-20 cells/mm³) may be seen in 5% of cases. However, a marked pleocytosis (>50 cells/mm³) should raise suspicion of an alternative etiology affecting the central nervous system or nerve roots, such as infection, inflammation, or a malignant neoplasm. Intravenous immunoglobulin therapy can increase CSF protein and white cell counts, complicating the interpretation of CSF after initiation of therapy. 

Electrophysiologic Studies

Electrodiagnostic studies, including nerve conduction studies and needle electromyography, can help support the diagnosis and exclude mimics, especially in atypical presentations. Electrodiagnostic findings can also help classify patients with classical GBS into 3 electrophysiological subtypes: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor-sensory axonal neuropathy (AMSAN). This differentiation may help with prognosis. 

The study results may be normal or nonspecific, particularly when performed early in the course of the illness (eg, within a week of presentation) or when the disease is very mild, slowly progressive, or primarily proximal. A repeat study may be needed in 1 to 3 weeks. Several sets of electrodiagnostic criteria suggest differentiation between subtypes based on characteristic electrodiagnostic changes in at least 2 motor nerves. However, all electrodiagnostic criteria have limitations, as subtypes can often be indistinguishable.[44]

Due to the involvement of proximal nerve roots or trunks, the demyelinating variants of GBS may have prolonged F-wave latency or absent F-waves and H-reflexes. As the disease progresses, motor nerves show increased distal latency and conduction block with temporal dispersion (prolonged distal compound muscle action potential [CMAP] duration of 8.5 ms).[45] A sural-sparing pattern, with preserved sural sensory nerve action potentials in the presence of affected upper-extremity sensory responses, suggests a non–length–dependent neuropathy and strengthens the suspicion of GBS.[46] Additional studies, such as prolonged blink reflex latencies, may be helpful in the bulbar-predominant presentation of the disease or when extremity responses are absent.[47]

In AMAN, distal CMAP amplitudes are reduced, whereas distal motor latencies and conduction velocities are preserved, without temporal dispersion. F-waves may be absent but are not significantly prolonged. In the AMSAN variant, both CMAP and sensory nerve action potential amplitudes are reduced. 

Neuroimaging

Magnetic resonance imaging of the neuraxis with contrast enhancement may help support the diagnosis of GBS, especially in the presence of red flags. Spinal MRI scans may show intrathecal thickening or enhancement of the spinal nerve roots or cauda equina with a high sensitivity.[48] Brain MRI may show increased T2 signal in the brainstem and basal ganglia in patients with Bickerstaff brainstem encephalitis, typically with little to no enhancement. In the Miller Fisher variant, enhancement of cranial nerves or the dorsal columns may be noted. Peripheral nerve ultrasonography can show enlarged cervical nerve roots early in the disease, with improvement in cross-sectional area on serial studies during the recovery phase. In addition, sparing of sensory nerves and transient enlargement of the vagus nerve may be present.[49]

Treatment / Management

Supportive care is the mainstay of GBS management. The presence of one of the following must prompt consideration of admission to the critical care unit:

• Dysautonomia (heart rate and blood pressure should be continually monitored)
• Bulbar dysfunction
• Severe or rapidly worsening weakness, especially of the neck and hip flexors
• Respiratory distress [50][51]
(B2)

Mechanical Intubation

The risk of mechanical ventilation is greatest with rapid disease progression, bulbar dysfunction, and neck or hip flexor weakness. Mechanical ventilation is indicated when signs of impending respiratory failure are present:

• Tachypnea
• Accessory muscle use
• Inability to count to 15 or more during the expiratory phase of a single full capacity breath
• Diminished cough strength
• 20/30/40 rule: Vital lung capacity <20 mL/kg, or a maximal inspiratory pressure <30 cm H₂O, or a maximal expiratory pressure <40 cm H₂O
• Hypercarbia (partial pressure of arterial carbon dioxide >48 mm Hg) or hypoxemia (partial pressure of arterial oxygen <56 mm Hg) 

Depolarizing neuromuscular blockers, such as succinylcholine, should be avoided during intubation, as they can precipitate hyperkalemia. Noninvasive ventilation is not recommended.[52](B3)

Rehabilitation

Physical therapy, occupational therapy, nutritional support, and speech-language pathology must be involved early.

Immunotherapy

Intravenous immunoglobulin and plasma exchange are equally effective in GBS. The choice should depend on factors like patient preference, local availability, cost, contraindications, and risk factors.[53][54] Intravenous immunoglobulin (IVIG) is generally preferred because it is better tolerated and easier to administer. These treatments do not prevent disease progression or reduce the extent of nerve damage, but can shorten the time to recovery, especially when initiated early. (A1)

Intravenous immunoglobulin is administered at a dose of 2 g/kg over 2 to 5 days. Adverse reactions include transfusion reactions, headaches, aseptic meningitis, liver dysfunction, acute kidney injury from sucrose-containing intravenous immunoglobulin products, thromboembolism from hyperviscosity, and, rarely, anaphylaxis in patients with IgA deficiency.

Plasma exchange is administered at a dose of 50 mL/kg plasma per session. Milder cases may require only 2 sessions, while moderate cases may benefit from 4 sessions. Severe cases require at least 4 sessions, while 6 sessions showed no additional benefit.[55] Complications include hypotension, transfusion reactions, sepsis, thrombocytopenia, impaired clotting parameters, hypocalcemia, and intravenous access issues. In general, plasma exchange should be avoided in patients with autonomic instability because large fluid shifts can lead to hypotension.(A1)

No clinical improvement from immunotherapy:

Approximately 40% of patients report no clinical improvement from immunotherapy after reaching a plateau (at about 4 weeks). These patients should be assessed for early supportive interventions like percutaneous endoscopic gastrostomy and tracheostomy if needed, and discharged to a rehabilitation facility. Neither redosing with a second course of IVIG nor combining IVIG with plasmapheresis, in either order, has proven beneficial in these patients. These approaches have been associated with a higher incidence of adverse events.[56][57](A1)

Initial clinical improvement from immunotherapy followed by worsening:

This group of patients either has treatment-related fluctuations or acute-onset CIDP and often responds to retreatment with the previously administered immunotherapeutic agent (for treatment-related fluctuations) or long-term immunosuppression (for acute-onset CIDP). The presence of facial weakness, dysautonomia, or the need for mechanical ventilation reduces the likelihood of CIDP. Conversely, the presence of prominent vibratory and proprioceptive impairments on physical examination favors a diagnosis of acute-onset CIDP.[58]

Corticosteroids

Results from multiple clinical trials demonstrate that corticosteroids are not beneficial in GBS and may result in worse clinical outcomes.[59] However, for immune checkpoint inhibitor–related GBS, IVIG (0.4 g/kg/d for 5 days) is concurrently administered with prednisolone (1-2 mg/kg/d) or intravenous methylprednisolone (1 g/d) for 5 days, followed by a steroid taper. (A1)

Emerging Treatments

Results from a phase 3 clinical trial reported that the C1q complement–blocking antibody (ANX005) improved the GBS disability scale, reduced time to walking independently, and reduced dependence on mechanical ventilation (ClinicalTrials.gov ID: NCT04701164). The initiating molecule of the classical complement pathway, C1q, prevents downstream activation of all complement components while leaving the lectin and alternative pathways intact to combat bacterial infections. 

Differential Diagnosis

The differential diagnosis is based on etiology and subclassified based on the part of the central or peripheral nervous system it impacts:

Infections

• Anterior horn cell: Poliovirus, enterovirus D68 or A71, Japanese encephalitis virus, West Nile virus, or rabies virus
• Nerve roots: Borrelia burgdorferi, cytomegalovirus, Epstein-Barr virus, HIV, or varicella zoster virus
• Peripheral nerves: Corynebacterium diphtheriae or HIV

Inflammation or autoimmune

• Central nervous system: Acute transverse myelitis, sarcoidosis, Sjögren disease
• Peripheral nerves: Chronic inflammatory demyelinating polyradiculoneuropathy, vasculitis
• Neuromuscular junction: Myasthenia gravis, Lambert-Eaton myasthenic syndrome
• Muscles: Inflammatory myositis

Nutritional

• Central nervous system: Wernicke encephalopathy due to deficiency of vitamin B1, or subacute combined degeneration of the spinal cord due to deficiency of vitamin B12
• Peripheral nervous system: Vitamins B1 (beriberi), B12, or E deficiency

Toxic or drug-induced

• Peripheral nerves: Toxicity from drugs, alcohol, lead, vitamin B6,  thallium, arsenic, organophosphate, methanol, diethylene glycol, ethylene glycol, or N-hexane
• Neuromuscular junction: Botulism, tick paralysis, tetanus, or snakebite envenomation; organophosphate poisoning
• Muscles: Drug-induced toxic myopathy induced by colchicine, chloroquine, emetine, or statins

Metabolic or Electrolyte Disturbances

• Peripheral nerves: Hypoglycemia, hypothyroidism, porphyria, or copper deficiency
• Muscles: Hypokalaemia, thyrotoxic hypokalemic periodic paralysis, hypomagnesemia, or hypophosphatemia

Vascular

• Central nervous system: Brainstem stroke, spinal cord stroke

Malignant neoplasms

• Central nervous system: Leptomeningeal metastasis, neurolymphomatosis
• Nerve roots: Leptomeningeal metastasis
• Peripheral nerves: Neurolymphomatosis

Miscellaneous

• Mitochondrial disorders affecting muscles or nerves
• Critical illness polyneuropathy or myopathy
• Functional neurologic disorder
• Compression of nerve roots, brainstem, or spinal cord
• Neuralgic amyotrophy [1]

Prognosis

Overall, long-term outcomes in GBS are favorable. More than 50% of patients recover fully within 1 year. After immunotherapy, 77% of patients ambulate independently at 6 months and 81% at 12 months.[4]

• Axonal GBS may continue to improve beyond 1 year, although some patients do not fully recover.
• A specific subtype of GBS associated with anti–pan-neurofascin antibodies has been identified with severe motor deficits, prolonged morbidity, respiratory insufficiency, but with a monophasic course and refractory to treatment.[60]
• Bickerstaff brainstem encephalitis can present with severe symptoms but is usually self-limiting and has a favorable prognosis. 
• Long-term disability is common and may include weakness, neuropathic pain, fatigue, and psychiatric symptoms such as grief and depression.
• Mortality rate ranges from 3% to 7% overall, and is approximately 20% for patients who require mechanical ventilation.[42][61]
• Sex does not seem to affect prognosis. 
• Advanced age, associated comorbidities, severe disease, cardiac and pulmonary complications, mechanical ventilation, and systemic infection are indicators of a higher mortality. Other predictors of poor outcome include antecedent C jejuni infection (especially if accompanied by diarrhea) and axonal electrophysiological subtypes.[4]
• Pulmonary embolism, acute respiratory distress syndrome, and infections are the most common causes of death. These events can occur not only in the acute phase but also during the recovery period, underscoring the need for continued supportive care.
• Serum neurofilament light chain levels measured during the acute phase have been suggested as a prognostic marker of functional independence 1 year after disease onset 1.[62]

Prognostic Models

There are 2 validated prognostic models, the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and the Modified Erasmus GBS Outcome Score (mEGOS), which help predict the probability of respiratory insufficiency within the first week of admission and the probability of being unable to walk independently during the first 6 months, respectively.[51][63]

EGRIS accounts for:

• Days between onset and hospital admission
• Facial and/or bulbar weakness
• Medical Research Council sum score

Modified EGOS* accounts for:

• Age at onset (years)
• Diarrhea before the onset of symptoms
• Medical Research Council sum score

*EGOS can be performed once at admission and on day 7. 

Complications

Patients with acute neuromuscular weakness are at risk for a wide range of complications affecting multiple organ systems. Immobility can lead to pressure palsies, ulcers, contractures, and thromboembolic events, while hospital-acquired complications such as pneumonia, urinary tract infections, delirium, and acute respiratory distress syndrome are common. Weakness of craniobulbar muscles increases the risk of dysphagia, corneal injury, aspiration, and respiratory failure. Autonomic dysfunction may manifest as labile blood pressure, arrhythmias, gastrointestinal dysmotility, and bladder or bowel disturbances. Additional complications include fatigue, paresthesias, pain, and psychological sequelae such as anxiety and depression.

Complications related to limb weakness (immobility):

• Pressure palsies
• Pressure ulcers
• Limb contractures
• Deep vein thrombosis
• Pulmonary embolism

Hospital-acquired complications:

• Pneumonia
• Urinary tract infections
• Delirium/hallucinations (especially in the ICU)
• Acute respiratory distress syndrome

Complications related to weakness of craniobulbar musculature:

• Dysphagia
• Corneal ulceration (from facial palsy)
• Aspiration pneumonia
• Respiratory failure 

Complications related to autonomic dysfunction:

• Labile blood pressure
• Cardiac arrhythmias
• Bowel or bladder dysfunction
• Gastrointestinal dysmotility (paralytic ileus)

Miscellaneous:

• Fatigue
• Paresthesias
• Pain
• Anxiety
• Depression