Neurology · PANCE / PANRE

Guillain-Barré Syndrome

Acute immune-mediated ascending demyelinating polyneuropathy; can cause respiratory failure.

Also known as: GBS, Guillain-Barré, acute inflammatory demyelinating polyneuropathy, AIDP, Miller Fisher syndrome

Overview

Acute, immune-mediated, predominantly demyelinating polyradiculoneuropathy causing rapidly progressive symmetric weakness, areflexia, and variable sensory and autonomic involvement. Most common subtype in Western countries is acute inflammatory demyelinating polyneuropathy (AIDP); axonal subtypes (AMAN, AMSAN) more common in Asia. Miller Fisher syndrome variant: ophthalmoplegia + ataxia + areflexia, associated with anti-GQ1b antibodies.

Epidemiology

Incidence ~1-2 per 100,000 per year. Affects all ages; slight male predominance. Most common cause of acute generalized weakness in developed countries.

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Question 1NeurologyMedium
A 22-year-old woman develops symmetric weakness that begins in her feet and ascends over several days, 3 weeks after an episode of Campylobacter gastroenteritis. On examination she has flaccid weakness with absent deep tendon reflexes and is developing difficulty breathing. Sensation is preserved. Cerebrospinal fluid analysis shows protein 180 mg/dL with a white blood cell count of 4/mm³. Which of the following is the most likely diagnosis?
  • AMyasthenia gravis
  • BTransverse myelitis
  • CMultiple sclerosis
  • DGuillain-Barré syndrome
Reveal answer & full explanation
Correct answer: D — Guillain-Barré syndrome
  • AMyasthenia gravis
  • BTransverse myelitis
  • CMultiple sclerosis
  • DGuillain-Barré syndrome

Why Guillain-Barré syndrome is correct

  • Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy) presents with ascending symmetric flaccid weakness and areflexia, often 1-3 weeks after Campylobacter jejuni gastroenteritis
  • Cerebrospinal fluid shows albuminocytologic dissociation — elevated protein (180 mg/dL) with a normal cell count (4/mm³)
  • Preserved sensation and early respiratory difficulty fit an evolving demyelinating polyneuropathy
  • Treatment is IVIG or plasmapheresis; corticosteroids are not effective

Why the others are wrong

  • Myasthenia gravis — causes fatigable weakness with normal reflexes and normal CSF, and is not triggered by an antecedent gastrointestinal infection (premature closure on weakness)
  • Transverse myelitis — produces a discrete sensory level with bowel/bladder involvement and CSF pleocytosis, none of which is present (confused-with-a-cord-syndrome)
  • Multiple sclerosis — a relapsing central demyelinating disease, not an acute ascending flaccid paralysis with areflexia after Campylobacter (buzzword-matching on "demyelination")
Question 2NeurologyMedium
A 58-year-old woman develops symmetric weakness that begins in her proximal legs and ascends over 10 days. On examination she has flaccid weakness, absent deep tendon reflexes, and labile blood pressure and heart rate. Cerebrospinal fluid analysis shows protein 420 mg/dL with a white blood cell count of 6/mm³. Nerve conduction studies show markedly reduced conduction velocities. Which of the following is the most important parameter to monitor?
  • AForced vital capacity
  • BSerum creatine kinase
  • CContinuous EEG
  • DSerial brain MRI
Reveal answer & full explanation
Correct answer: A — Forced vital capacity
  • AForced vital capacity
  • BSerum creatine kinase
  • CContinuous EEG
  • DSerial brain MRI

Why Forced vital capacity is correct

  • The ascending flaccid weakness, areflexia, autonomic instability, albuminocytologic dissociation, and slowed conduction velocities indicate Guillain-Barré syndrome
  • The major life threat is neuromuscular respiratory failure, so serial forced vital capacity (with negative inspiratory force) guides the need for intubation
  • A falling FVC toward roughly 20 mL/kg signals impending respiratory failure before oxygen saturation drops
  • IVIG or plasmapheresis is the treatment; corticosteroids are ineffective

Why the others are wrong

  • Serum creatine kinase — tracks muscle breakdown in myopathies and has no role in monitoring respiratory status in a neuropathy (confused-with-a-myopathy)
  • Continuous EEG — monitors for seizures, which are not a feature of this peripheral process (buzzword-matching on a neurologic monitor)
  • Serial brain MRI — Guillain-Barré syndrome is a peripheral disease, so brain imaging does not track its life-threatening complication (anchoring on central imaging)
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Risk factors

  • Antecedent infection (~2/3 of cases, 1-4 weeks before onset):
  • Campylobacter jejuni (most common; associated with AMAN axonal variant and anti-GM1 antibodies)
  • Cytomegalovirus
  • Epstein-Barr virus
  • Mycoplasma pneumoniae
  • Influenza
  • Zika virus
  • SARS-CoV-2 (associations reported)
  • Vaccinations (rare; modest signal historically with swine flu 1976; small risk with some vaccines)
  • Surgery, malignancy (rare)

Pathophysiology

Molecular mimicry: antibodies generated against pathogen surface antigens cross-react with epitopes on peripheral nerve myelin (gangliosides — GM1, GD1a, GQ1b). Complement activation and macrophage-mediated demyelination produce conduction block. Axonal subtypes target the nodes of Ranvier and axolemma directly. Resolves over weeks-months as nerve remyelinates.

Clinical presentation

Symptoms

  • Symmetric ascending weakness beginning in the legs, progressing over hours to days (peak by 2-4 weeks)
  • Distal paresthesias and pain (often missed by clinicians but very common — back pain especially)
  • Areflexia or hyporeflexia (key feature)
  • Cranial nerve involvement in ~50% — bilateral facial weakness, dysphagia, dysarthria
  • Respiratory muscle weakness — 25% require mechanical ventilation
  • Autonomic dysfunction: tachy/bradyarrhythmias, BP swings, ileus, urinary retention
  • Miller Fisher variant: ophthalmoplegia, ataxia, areflexia (anti-GQ1b)

Signs / physical exam

  • Symmetric weakness, often distal>proximal initially, progressing to flaccid paralysis
  • Decreased or absent deep tendon reflexes
  • Mild distal sensory loss; rarely sensory level
  • Bilateral facial weakness (peripheral CN VII pattern)
  • Respiratory: tachypnea, paradoxical breathing, decreased forced vital capacity (NIF/MIP)
  • Autonomic instability

Classic findings

Acute ascending symmetric weakness + areflexia + antecedent infection + albuminocytologic dissociation in CSF (elevated protein with normal cell count).

Differential diagnosis

  • Spinal cord compression / transverse myelitis — Sensory level, bowel/bladder early, upper motor neuron signs — MRI spine mandatory
  • Myasthenia gravis — Fatigability, ocular/bulbar predominance, normal reflexes, AChR antibodies; not ascending
  • Botulism — Descending paralysis, dilated pupils, dry mucous membranes (anticholinergic effect on autonomic nerves), recent home-canned food or honey (infants)
  • Tick paralysis — Tick attached; rapid recovery after removal
  • Lyme disease (Bannwarth syndrome) — Painful radiculopathy, facial palsy, erythema migrans history
  • Acute intermittent porphyria — Abdominal pain, neuropsychiatric symptoms, dark urine, low motor function
  • Critical illness polyneuropathy/myopathy — Develops in ICU patients with sepsis/multiorgan failure
  • Heavy metal toxicity (lead, thallium, arsenic) — Subacute course, sensory >> motor, exposure history
  • Toxic neuropathies / drug-induced — Vincristine, isoniazid, statins; medication history

Diagnostic workup

Diagnostic criteria

Clinical: progressive symmetric weakness + areflexia, peak by 4 weeks, exclusion of alternative causes. Supportive: CSF albuminocytologic dissociation, electrodiagnostic features of demyelination.

Labs

  • CBC, BMP, LFTs, ESR, CRP, HIV, HBV, HCV
  • Antiganglioside antibodies (anti-GM1, anti-GD1a, anti-GQ1b — Miller Fisher)
  • Stool for Campylobacter (low yield, usually cleared by presentation)
  • Heavy metal screen if exposure history
  • Pulmonary function: bedside NIF (negative inspiratory force) and FVC every 4-8 h; intubate if FVC <20 mL/kg, NIF less negative than -30 cm H2O, or MEP <40 cm H2O ('20/30/40 rule')

Imaging

  • MRI spine with gadolinium — exclude compressive lesion; nerve root enhancement (especially cauda equina) supports GBS
  • Nerve conduction studies / EMG: slowed conduction velocities, prolonged distal latencies, conduction block, F-wave abnormalities (early), low amplitudes (axonal variants)
  • Lumbar puncture: albuminocytologic dissociation (elevated protein, normal WBC <5 cells/μL) — may be normal in first week; cell count >50 suggests alternate diagnosis (HIV, sarcoid, lymphomatous infiltration)

Diagnostic algorithm

FeatureGBSMyasthenia GravisBotulism
PatternAscending symmetricFatigable, ocular/bulbarDescending
ReflexesDecreased/absent (early)NormalDecreased
PupilsNormal (autonomic instability)NormalDilated, sluggish
AntecedentInfection 1-4 wk priorInsidiousCanned food, honey (infants)
CSF↑ protein, normal cellsNormalNormal
EMGDemyelinating, conduction blockDecremental on repetitive stimIncremental on rapid repetitive stim
TreatmentIVIG or PLEX (not steroids)Pyridostigmine, immunosuppressionAntitoxin, supportive
Distinguishing GBS from other acute neuromuscular weakness.

Treatment

First-line

  • ICU admission for any patient with autonomic instability, bulbar weakness, or rapidly progressive disease
  • Frequent pulmonary monitoring (FVC, NIF q4-8h); intubate at 20/30/40 thresholds — do not wait for hypoxia
  • IVIG 0.4 g/kg/day × 5 days (total 2 g/kg) — first-line, equivalent efficacy to PLEX, easier to administer
  • Plasma exchange (plasmapheresis) — 5 exchanges over 1-2 weeks; alternative first-line
  • Combining IVIG and PLEX provides NO additional benefit
  • Corticosteroids are NOT effective and may be harmful — do not use
  • Supportive: DVT prophylaxis, pain control (gabapentin, opioids — neuropathic pain common), bowel/bladder care, pressure ulcer prevention, PT/OT

Second-line / adjunct

  • Treat autonomic dysfunction: cautious BP management (avoid sudden drops), pacemaker pads available for bradyarrhythmias
  • Nutrition: NG/PEG if dysphagia
  • Psychological support (locked-in syndrome possible during peak)
  • Long inpatient rehab often required
  • Most patients improve over weeks-months; ~80% walk independently by 6 months

Complications

  • Respiratory failure requiring mechanical ventilation (~25%)
  • Autonomic dysfunction with fatal arrhythmias
  • DVT/PE from immobility
  • Pneumonia (aspiration, ventilator-associated)
  • Decubitus ulcers
  • Chronic pain (persistent in some patients)
  • Residual weakness in ~20% at one year
  • Mortality 3-5%, mostly from respiratory or autonomic complications
  • Recurrence rare (~3%); persistent worsening >8 weeks → consider CIDP

PANCE pearls

  • Loss of reflexes early is a defining feature — preserved reflexes argues against GBS.
  • Albuminocytologic dissociation: elevated CSF protein with normal cell count. Pleocytosis (>5-10 WBC) should make you reconsider GBS — think HIV, Lyme, sarcoid, lymphomatous meningitis.
  • 20/30/40 rule for intubation: FVC <20 mL/kg, NIF less negative than -30, or MEP <40 cm H2O.
  • Steroids do NOT work in GBS — use IVIG or PLEX.
  • Miller Fisher variant: ophthalmoplegia + ataxia + areflexia + anti-GQ1b antibodies. Usually self-limited.
  • Persistent or progressive weakness >8 weeks moves the diagnosis to CIDP — which DOES respond to steroids.

References

  • AAN 2003 / 2012 update — Practice Parameter: Immunotherapy for Guillain-Barré Syndrome (Hughes et al., Neurology 2003; reaffirmed)
  • GBS Consensus — Diagnosis and Management of Guillain-Barré Syndrome — International Consensus Guideline (Leonhard et al., Nat Rev Neurol 2019)
  • Cochrane IVIG — Intravenous Immunoglobulin for Guillain-Barré Syndrome (Hughes et al., Cochrane Database 2014)
  • Brighton Criteria — Guillain-Barré Syndrome and Variants — Brighton Collaboration Case Definitions (Sejvar et al., Vaccine 2011)

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