Guillain-Barre Syndrome: Diagnosis and Management

Introduction

Guillain-Barre syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy - inflammation affecting peripheral nerve roots and nerves - causing rapidly progressive, usually ascending weakness. It is the commonest cause of acute flaccid paralysis worldwide and a genuine neurological emergency, since respiratory muscle involvement can develop within days and progress to ventilatory failure.¹

The classic story is a patient who had a gastrointestinal or respiratory infection 1-3 weeks earlier, now presenting with progressive limb weakness that starts distally in the legs and ascends. Recognising this pattern, and understanding why serial respiratory monitoring (not oxygen saturation alone) is the single most important safety measure, are the two things most consistently tested.

Incidence is roughly 1-2 per 100,000 per year, rising with age and slightly more common in men. Around two-thirds of patients report a preceding infection in the preceding six weeks, most often gastrointestinal or respiratory. The absence of an identifiable preceding illness, however, does not argue against the diagnosis, since a substantial minority have no recognised trigger - the diagnosis rests on the clinical pattern rather than on finding an antecedent infection.

Aetiology and pathophysiology

GBS is thought to result from molecular mimicry: an immune response to a preceding infection cross-reacts with epitopes on peripheral nerve myelin or axonal membranes, because of structural similarity between microbial antigens and nerve components (particularly gangliosides).

The location of the target antigen determines the clinical variant, which is why the subtypes below are more than taxonomy. Antibodies directed at myelin or the Schwann cell surface produce a demyelinating picture with conduction slowing and block, and because myelin can be repaired relatively quickly, recovery tends to be faster. Antibodies directed at axonal membrane gangliosides - typically after Campylobacter, whose lipo-oligosaccharide closely mimics human GM1 - produce an axonal picture, where recovery depends on slow axonal regeneration and is correspondingly more prolonged and less complete.

The same principle explains Miller Fisher syndrome. Anti-GQ1b antibodies bind an antigen that is particularly densely expressed in the nerves supplying the extraocular muscles, which is precisely why that variant presents with ophthalmoplegia rather than limb weakness.

• Campylobacter jejuni - the most commonly identified preceding infection, particularly associated with the axonal variant and a worse prognosis
• Other preceding infections: cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, Zika virus, and respiratory or gastrointestinal viral illnesses generally
• Vaccination - a very small increase in risk has been described after some vaccines (historically noted with certain influenza vaccines), though the increase in risk is far smaller than the risk from the infections vaccines prevent
• Surgery - can occasionally precede GBS
• In many cases, no clear preceding trigger is identified

Clinical features

• Ascending, symmetric limb weakness - classically starting in the distal legs and progressing proximally and upward over days, though the pattern and speed of progression vary
• Reduced or absent deep tendon reflexes (areflexia) - a key and near-universal examination finding
• Sensory symptoms - often present (paraesthesiae, mild sensory disturbance) but typically less prominent than the motor weakness, and objective sensory loss on examination may be minimal
• Back and limb pain - common, sometimes severe, and can precede weakness
• Bulbar and facial weakness - facial diplegia, dysphagia and dysarthria occur in a significant proportion
• Respiratory muscle weakness - can progress to ventilatory failure, sometimes rapidly
• Autonomic dysfunction - labile blood pressure, arrhythmias, urinary retention, ileus - can be life-threatening in its own right and needs cardiac monitoring in more severe cases
• Progression typically over days to a maximum of 4 weeks, followed by a plateau phase and then gradual recovery
• Miller Fisher variant: the triad of ophthalmoplegia, ataxia and areflexia, often with relatively preserved limb strength

Clinical examination

• Power - symmetric weakness, usually more marked distally early on but can become proximal-dominant as it evolves
• Reflexes - reduced or absent throughout, an essential finding to check and document
• Sensation - may be relatively preserved or show only mild distal impairment, distinguishing it from more sensory-predominant neuropathies
• Cranial nerves - facial weakness (often bilateral), bulbar function, and eye movements (for Miller Fisher variant)
• Respiratory assessment - respiratory rate, effort, ability to count to 20 in one breath as a rough bedside guide, and formal forced vital capacity measurement
• Autonomic assessment - heart rate and rhythm, blood pressure (including postural change), bladder function

Differential diagnosis

• Transverse myelitis or spinal cord compression - usually has a sensory level and sphincter involvement early, with reflexes that may initially be brisk rather than absent; MRI spine helps distinguish
• Myasthenia gravis - fatigable weakness without sensory symptoms and with preserved reflexes
• Botulism - descending paralysis with prominent autonomic and pupillary involvement
• Hypokalaemic or other periodic paralysis - acute weakness with a clear electrolyte abnormality
• Acute intermittent porphyria - can cause an acute motor neuropathy with abdominal pain and neuropsychiatric features
• Tick paralysis - rapidly progressive ascending paralysis resolving after tick removal
• Critical illness polyneuropathy - occurs in the context of prolonged critical illness rather than a preceding community infection
• Functional (non-organic) weakness

Investigations

Investigation supports the clinical diagnosis and helps exclude mimics; treatment should not be delayed while awaiting confirmatory results if the clinical picture and respiratory risk demand urgent action.

A practical bedside tool worth knowing is the 20/30/40 rule, used as a trigger for escalation: forced vital capacity below 20 mL/kg, maximum inspiratory pressure weaker than 30 cmH2O, or maximum expiratory pressure below 40 cmH2O all indicate that respiratory failure is approaching and that intensive care review is needed. Where formal spirometry is not immediately available, asking the patient to count aloud in a single breath gives a rough guide, as each number counted corresponds very approximately to 100 mL of vital capacity.

Blood gases are a poor substitute for these measures. A patient with neuromuscular respiratory failure maintains normal oxygenation and even a low PaCO2 through increased effort until they abruptly decompensate, so a reassuring gas can create false confidence right up to the point of arrest.

• Lumbar puncture - classically shows albuminocytological dissociation: a raised CSF protein with a normal or only mildly raised white cell count; may be normal in the first week, so a normal early result does not exclude GBS
• Nerve conduction studies - show a demyelinating pattern (slowed conduction velocity, conduction block) in AIDP, or reduced amplitude with preserved velocity in the axonal variants; can be normal very early in the illness
• Anti-ganglioside antibodies - anti-GM1 associated with axonal variants and preceding Campylobacter infection; anti-GQ1b strongly associated with Miller Fisher syndrome
• Serial forced vital capacity - the single most important monitoring test, performed regularly (for example every 4-6 hours in evolving disease) to detect respiratory compromise before it becomes critical
• ECG and cardiac monitoring - for autonomic instability and arrhythmia
• MRI spine - if there is diagnostic uncertainty with cord compression or transverse myelitis
• Stool culture - if Campylobacter infection is suspected from the preceding history

Management

Disease-specific treatment

IV immunoglobulin (IVIG) or plasma exchange are equally effective and are the mainstays of treatment, ideally started within 2 weeks of symptom onset (earlier is generally better) in anyone unable to walk unaided or with significant progression.² Combining the two, or switching from one to the other, is not routinely recommended.³

Supportive care

• Respiratory support - elective intubation and ventilation before respiratory failure becomes an emergency, guided by serial FVC and clinical assessment
• Cardiac monitoring - for autonomic instability and arrhythmia, particularly in more severe disease
• VTE prophylaxis - immobile patients are at significant risk
• Pain management - neuropathic pain (gabapentin, pregabalin, or amitriptyline) and analgesia for the often severe back/limb pain
• Bladder and bowel care - for autonomic dysfunction
• Early involvement of physiotherapy and occupational therapy, continuing throughout recovery, which can be prolonged
• Psychological support - the experience of rapidly progressive paralysis, sometimes requiring ventilation, is highly distressing and needs active support

Complications

• Respiratory failure requiring mechanical ventilation - occurs in a substantial minority
• Autonomic dysfunction - arrhythmias, labile blood pressure, which can be life-threatening
• Venous thromboembolism from immobility
• Aspiration pneumonia from bulbar weakness
• Chronic pain and fatigue during recovery
• Persistent weakness or sensory disturbance in those who do not fully recover
• Psychological sequelae - anxiety, depression, post-traumatic stress, particularly after a ventilated admission

Red flags

Prognosis

Most patients with GBS eventually make a good recovery, though this can take many months to a few years, and recovery is generally slower after axonal variants than after the demyelinating form. A significant minority are left with residual weakness, sensory disturbance, or fatigue, and a small proportion die, usually from complications such as respiratory failure, autonomic instability, or venous thromboembolism rather than the neuropathy itself. Poor prognostic factors include older age, rapid progression to severe weakness, need for ventilation, and an axonal rather than demyelinating pattern on nerve conduction studies.

Recovery is typically slow and non-linear, and setting expectations early prevents a great deal of distress. Weakness reaches its nadir within four weeks by definition, then plateaus for days to weeks before improvement begins - so a patient who is not improving in week three is usually following the expected course rather than deteriorating. Because axons regenerate at roughly a millimetre a day, distal recovery lags well behind proximal recovery, and residual foot drop or intrinsic hand weakness is common even in patients who otherwise do well.

Persistent fatigue and neuropathic pain are the two symptoms most often underestimated, frequently outlasting the weakness by months and having a disproportionate effect on return to work. Around 5-10% of patients experience a treatment-related fluctuation - deterioration after initial improvement - which usually responds to a further course of immunoglobulin, but a patient who continues to deteriorate beyond eight weeks should be reassessed for CIDP, which is treated differently and requires ongoing rather than one-off immunotherapy.

Two practical points about treatment are worth noting. Immunoglobulin and plasma exchange are equally effective, and the choice is usually made on availability, venous access and comorbidity rather than efficacy - immunoglobulin is simpler to give but carries a risk of thrombosis, renal impairment and, rarely, aseptic meningitis, while plasma exchange requires large-bore access and is less well tolerated in cardiovascular instability. Corticosteroids, notably, are ineffective in GBS and should not be given, in contrast to CIDP where they are a mainstay - a distinction that is frequently tested.