Guillain-Barré syndrome (GBS)

A 42-year-old man presents to the emergency department with progressive weakness in both legs and tingling in the feet over the past 4 days. The weakness has ascended over the past 24 hours, now involving the arms and causing difficulty swallowing. He reports an episode of bloody diarrhea 2 weeks earlier after consuming poultry, raising suspicion for antecedent Campylobacter jejuni gastroenteritis. On examination, there is bilateral symmetric weakness with a Medical Research Council (MRC) grade of 3/5 and absent deep tendon reflexes. Cerebrospinal fluid analysis shows elevated protein with a normal cell count. Electrophysiologic studies demonstrate prolonged latencies and decreased conduction velocities, consistent with a demyelinating pattern. MRI of the brain and spinal cord is normal. Diagnosis?

Diagnosis is Guillain-Barré syndrome with a demyelinating electrophysiologic pattern, most consistent with acute inflammatory demyelinating polyradiculoneuropathy, following recent gastroenteritis likely due to Campylobacter jejuni.

1. Definition

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy characterized by rapidly progressive, usually symmetric limb weakness with reduced or absent deep tendon reflexes.

GBS is a neurologic emergency because weakness may rapidly involve the respiratory muscles, bulbar muscles, and autonomic nervous system.

The principal electrophysiologic subtypes include:

1.      Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

2.      Acute motor axonal neuropathy (AMAN)

3.      Acute motor-sensory axonal neuropathy (AMSAN)

In this patient, the electrophysiologic findings are most consistent with AIDP.

2. Etiology and Precipitating Factors

1.      Approximately two-thirds of patients report an antecedent infection, usually involving the respiratory or gastrointestinal tract.

2.      Campylobacter jejuni is one of the best-established antecedent infections and is an important cause of postinfectious GBS.

3.      GBS usually develops within several days to a few weeks after the antecedent infection.

4.      Other associated infections include:

1.      Cytomegalovirus

2.      Epstein-Barr virus

3.      Mycoplasma pneumoniae

4.      Hepatitis E virus

5.      Zika virus

6.      Human immunodeficiency virus

5.      GBS may also occur after surgery or other immune-provoking events.

6.      In many patients, no specific preceding trigger is identified.

In this case, the history of bloody diarrhea following poultry consumption is compatible with Campylobacter jejuni infection, but the organism cannot be considered microbiologically confirmed from the clinical history alone.

3. Pathophysiology

1.      GBS results from an aberrant immune response directed against components of peripheral nerves and nerve roots.

2.      Molecular mimicry is particularly well established following Campylobacter jejuni infection.

3.      Certain Campylobacter antigens resemble gangliosides present in peripheral nerves.

4.      Cross-reactive antiganglioside antibodies may activate complement and disrupt nodal or axonal structures.

5.      This mechanism is particularly well established in axonal forms of GBS, including AMAN, which are associated with antibodies such as anti-GM1 and anti-GD1a.

6.      The immunopathogenesis of AIDP is more heterogeneous and primarily results in inflammatory segmental demyelination of peripheral nerves and nerve roots.

7.      Secondary axonal degeneration may occur in severe AIDP.

8.      Demyelination can produce slowed conduction velocity, prolonged distal motor latencies, conduction block, temporal dispersion, and prolonged or absent F waves.

4. Clinical Features

4.1 Motor Features

1.      Rapidly progressive bilateral weakness

2.      Weakness commonly begins in the lower extremities and progresses upward.

3.      Areflexia or hyporeflexia is characteristic.

4.      Upper limb and truncal weakness may develop as the disease progresses.

5.      Severe disease may involve the respiratory muscles, resulting in respiratory failure.

Most patients reach their clinical nadir within approximately 2 weeks, and progression generally reaches its nadir within 4 weeks.

4.2 Sensory Features

1.      Distal paresthesias

2.      Tingling or numbness of the hands and feet

3.      Neuropathic or radicular pain

4.      Back pain

5.      Objective sensory loss is generally less prominent than motor weakness.

4.3 Cranial Nerve and Bulbar Involvement

1.      Facial weakness, often bilateral

2.      Dysphagia

3.      Dysarthria

4.      Weakness of pharyngeal and other bulbar muscles

5.      Ophthalmoplegia may occur, particularly in variants such as Miller Fisher syndrome.

Bulbar weakness is clinically important because it increases the risk of aspiration and respiratory deterioration.

4.4 Autonomic Dysfunction

Autonomic involvement may be significant and potentially life-threatening.

Manifestations include:

1.      Labile blood pressure

2.      Tachycardia

3.      Bradycardia

4.      Cardiac arrhythmias

5.      Abnormal sweating

6.      Urinary retention

7.      Ileus

8.      Other disturbances of cardiovascular autonomic control

5. Diagnostic Evaluation

5.1 Clinical Diagnosis

GBS is primarily a clinical diagnosis supported by cerebrospinal fluid and electrophysiologic findings.

Characteristic features include:

1.      Progressive bilateral limb weakness

2.      Reduced or absent deep tendon reflexes

3.      Progression over days to several weeks

4.      Relative symmetry of weakness

5.      Cranial nerve, sensory, respiratory, or autonomic involvement may provide additional support.

The combination in this patient of rapidly ascending symmetric weakness, areflexia, dysphagia, a recent diarrheal illness, albuminocytologic dissociation, and demyelinating electrophysiologic abnormalities is strongly supportive of GBS.

5.2 Cerebrospinal Fluid Analysis

The characteristic CSF abnormality is albuminocytologic dissociation, consisting of:

1.      Elevated CSF protein

2.      Normal or only mildly increased white blood cell count

Important considerations include:

1.      CSF protein may remain normal early in the illness, particularly during the first week.

2.      Therefore, a normal CSF protein concentration early in the disease does not exclude GBS.

3.      Mild CSF pleocytosis can occasionally occur.

4.      A more substantial pleocytosis, particularly greater than 50 cells/µL, should prompt careful evaluation for an alternative infectious, inflammatory, or malignant diagnosis.

5.3 Electrophysiologic Studies

Nerve conduction studies and electromyography support the diagnosis and help characterize the electrophysiologic pattern.

Findings supporting a demyelinating pattern include:

1.      Reduced conduction velocity

2.      Prolonged distal motor latency

3.      Prolonged or absent F waves

4.      Conduction block

5.      Temporal dispersion

Important considerations include:

1.      Electrophysiologic studies may be normal or nondiagnostic early in the disease.

2.      Repeat testing may therefore be appropriate when clinical suspicion remains high.

3.      Electrophysiologic subtype classification has limitations, particularly early in the disease, and serial studies may occasionally alter the apparent classification.

4.      Axonal patterns may be present in AMAN or AMSAN.

5.4 MRI

1.      MRI is not required to establish the diagnosis in a typical case of GBS.

2.      MRI of the brain and spinal cord parenchyma is often normal.

3.      Contrast-enhanced spinal MRI may demonstrate enhancement of the spinal nerve roots or cauda equina, although this finding is not specific for GBS.

4.      MRI is particularly useful when an alternative diagnosis such as spinal cord compression, transverse myelitis, or another structural lesion must be excluded.

5.5 Antiganglioside Antibodies

1.      Routine antiganglioside antibody testing has limited diagnostic value in typical motor-sensory GBS.

2.      Specific antibodies are associated with particular GBS subtypes.

3.      Anti-GQ1b antibodies are strongly associated with Miller Fisher syndrome and related disorders.

4.      Antibodies against GM1 and GD1a are more frequently associated with axonal forms of GBS, particularly after Campylobacter jejuni infection.

5.6 Distinguishing GBS From Acute-Onset CIDP

GBS generally reaches its clinical nadir within 4 weeks.

Acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered when:

1.      Neurological deterioration continues or recurs more than 8 weeks after symptom onset, or

2.      There are three or more treatment-related fluctuations.

A-CIDP cannot be confirmed solely because progression lasts slightly longer than 4 weeks.

6. Management

6.1 Hospitalization and Intensive Monitoring

Patients with suspected GBS generally require hospital admission because deterioration may occur rapidly.

Intensive care or high-acuity monitoring should be considered when there is:

1.      Rapid progression of weakness

2.      Bulbar dysfunction

3.      Respiratory muscle weakness

4.      Weak cough or inability to clear secretions

5.      Significant autonomic instability

6.      Rapidly declining respiratory measurements

7.      High predicted risk of mechanical ventilation

The presence of rapidly ascending weakness and dysphagia in this patient requires particularly close respiratory and bulbar monitoring.

6.2 Immunotherapy

The two established disease-modifying treatments are:

1.      Intravenous immunoglobulin (IVIG)

2.      Plasma exchange

For patients unable to walk independently, the standard IVIG regimen is:

IVIG 0.4 g/kg/day for 5 consecutive days

Plasma exchange is an effective alternative and is generally administered as:

Four to five exchanges, with a total exchanged volume of approximately 12 to 15 L, over 1 to 2 weeks

IVIG and plasma exchange have comparable efficacy when appropriately administered.

Patients who remain ambulatory but have rapid clinical deterioration, swallowing difficulty, autonomic dysfunction, risk of respiratory failure, or other poor prognostic features may also warrant immunotherapy.

Given this patient's rapid progression, upper limb involvement, and dysphagia, prompt treatment with IVIG or plasma exchange is appropriate.

6.3 Treatments That Should Not Be Used Routinely

1.      Corticosteroids are not effective as disease-modifying therapy for GBS.

2.      Routine sequential treatment with plasma exchange followed immediately by IVIG is not recommended.

3.      Routine use of a second course of IVIG solely because a patient has a predicted poor prognosis is not recommended.

4.      Failure to improve immediately after the first course of therapy does not by itself justify routine sequential treatment with the alternative therapy.

A true treatment-related fluctuation is a separate clinical situation and may warrant retreatment after specialist reassessment.

6.4 Respiratory Monitoring

Respiratory deterioration may occur rapidly and should be assessed serially.

Monitoring should include:

1.      Forced vital capacity (FVC)

2.      Clinical assessment of respiratory effort

3.      Ability to cough and clear secretions

4.      Bulbar function

5.      Single-breath count when appropriate

6.      Inspiratory and expiratory respiratory muscle strength when available

Important warning signs include:

1.      FVC at or below approximately 20 mL/kg

2.      A substantial or rapidly progressive decline in FVC

3.      Severe bulbar weakness

4.      Ineffective cough

5.      Increasing work of breathing

6.      Other evidence of impending ventilatory failure

Elective intubation should be considered before overt respiratory collapse develops.

Pulse oximetry alone is insufficient for early detection of neuromuscular respiratory failure, because oxygen saturation may remain normal until respiratory weakness is advanced.

The modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) can assist in estimating the risk of mechanical ventilation.

7. Supportive Care

Supportive management is essential and includes:

1.      Respiratory support when required

2.      Monitoring and treatment of autonomic instability

3.      Cardiac monitoring when significant dysautonomia is present

4.      Assessment of swallowing and appropriate aspiration precautions

5.      Nutritional support when swallowing is impaired

6.      Venous thromboembolism prophylaxis in immobilized patients when not contraindicated

7.      Physical and occupational therapy

8.      Prevention of pressure injuries

9.      Management of bowel and bladder dysfunction

10.  Treatment of neuropathic and musculoskeletal pain

11.  Prevention and treatment of hospital-acquired complications

8. Complications

8.1 Respiratory Failure

Progressive respiratory muscle weakness may require invasive mechanical ventilation.

8.2 Autonomic Instability

Severe dysautonomia may cause:

1.      Marked fluctuations in blood pressure

2.      Bradyarrhythmias

3.      Tachyarrhythmias

4.      Potentially life-threatening cardiovascular instability

8.3 Aspiration and Pneumonia

Bulbar weakness and impaired airway protection increase the risk of aspiration and pneumonia.

8.4 Venous Thromboembolism

Prolonged immobility increases the risk of deep vein thrombosis and pulmonary embolism.

8.5 Persistent Neurologic Symptoms

Some patients experience persistent:

1.      Weakness

2.      Fatigue

3.      Neuropathic pain

4.      Sensory symptoms

5.      Reduced exercise tolerance

9. Prognosis

1.      Most patients experience substantial neurological recovery, although recovery may take weeks to months.

2.      Approximately 80% of treated patients are able to walk independently by 6 months.

3.      Approximately 20% of treated patients remain unable to walk independently at 6 months.

4.      Overall mortality is approximately 5%.

5.      Death may result from respiratory failure, cardiovascular autonomic complications, infection, thromboembolism, or other systemic complications.

6.      Neurological recovery may continue for a year or longer.

7.      Residual fatigue, weakness, sensory symptoms, or pain may persist even after independent ambulation has returned.

8.      Prognosis can be estimated using the modified Erasmus GBS Outcome Score (mEGOS).

10. Key Clinical Insight

Rapidly progressive symmetric ascending weakness with areflexia, distal paresthesias, bulbar involvement, recent gastroenteritis, albuminocytologic dissociation, and demyelinating nerve conduction abnormalities is highly characteristic of Guillain-Barré syndrome.

In this patient, the electrophysiologic findings are most consistent with AIDP. The preceding bloody diarrheal illness after poultry exposure makes Campylobacter jejuni a likely antecedent trigger, although microbiological confirmation is not provided.

Because the patient has rapid progression and dysphagia, close monitoring for respiratory failure and autonomic instability is essential, and prompt treatment with IVIG or plasma exchange is appropriate.

References

1.      van Doorn PA, Van den Bergh PYK, Hadden RDM, et al. European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome. Eur J Neurol. 2023;30(12):3646-3674. doi:10.1111/ene.16073.

2.      Leonhard SE, Papri N, Querol L, Rinaldi S, Shahrizaila N, Jacobs BC. Guillain-Barré syndrome. Nat Rev Dis Primers. 2024;10(1):97. doi:10.1038/s41572-024-00580-4.

3.      Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barré syndrome. Lancet. 2021;397(10280):1214-1228. doi:10.1016/S0140-6736(21)00517-1.