II. Definition
- Progressive, idiopathic, symmetrical weakness and loss of Deep Tendon Reflexes reaching maximal intensity within 4 weeks
III. Epidemiology
IV. Precautions
- Presentation may have subtle, non-specific findings early in the course
- Focal Paresthesias
- Perception of weakness without motor weakness on exam
- Deep Tendon Reflexes may initially be preserved, and may appear to be asymmetric
V. Pathophysiology
- Inflammatory Neuropathy with cross reactivity between antibodies to infectious agents and neural Antigens
- Lipooligosaccharides in Bacterial cell wall resemble gangliosides
- Anti-ganglioside antibodies form in response to acute infections (e.g. Diarrhea with Campylobacter jejuni)
VI. Types: Most Common Subtypes
- Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)
- Most common subtype in the United States (90% of cases)
- Multifocal peripheral demyelination with slow remyelination
- Presents with progressive symmetrical weakness and hyporeflexia
- Symptoms start in legs in 90% of cases
- Myelin predominantly injured
- Acute Motor Axonal Neuropathy (AMAN)
- Accounts for 5-10% of Guillain-Barre Syndrome cases in U.S.
- Anti-ganglioside antibodies (GM1, GD1a, GalNAc-GD1a, GD1b) bind in peripheral Motor Nerve axons
- Most associated with Campylobacter jejuni infection (esp. younger patients, summer, China and Japan)
- Pure motor Neuropathy
- No demyelination (contrast with AIDP)
- Nodes of Ranvier predominantly injured
- Acute Motor Sensory Axonal Neuropathy (AMSCAN)
- Similar to AMAN subtype, but sensory Neuropathy predominates
VII. Types: Rare Subtypes
- Miller Fisher Syndrome (3% of cases)
- Anti-ganglioside antibodies (GQ1b, GD3, GT1a)
- Bilateral Ophthalmoplegia, Ataxia and areflexia
- Facial or bulbar weakness (50% of cases)
- Trunk and extremity weakness (50% of cases)
- Acute Panautonomic Neuropathy (rarest)
- Autonomic symptoms (cardiovascular and visual)
- Sensory loss
- Slow, often incomplete recovery
VIII. Risk Factors
- Acute infection precedes Guillain-Barre in 66% of cases
- Campylobacter jejuni (most common)
- Guillain-Barre occurs in one in 1000 patient infected with Campylobacter jejuni
- Epstein-Barr Virus (Mononucleosis)
- Associated with milder forms of Guillain-Barre
- Mycoplasma pneumoniae
- HaemophilusInfluenzae
- Cytomegalovirus
- HIV Infection
- Varicella Zoster Virus
- Vector-Borne Infections (Mosquito borne)
- Campylobacter jejuni (most common)
-
Vaccinations are associated with no significant increased risk
- H1N1 Influenza Vaccine was associated with a risk of 1-2 cases per 1 Million
- Tetanus Vaccine and hepatitis Vaccines also have minimal increased risk
- De Wals (2012) JAMA 308(2): 175-81 [PubMed]
IX. Course
- Peak timing
- Peaks by 2 weeks in 50% of cases
- Peaks by 3 weeks in 80% of cases
- Peaks by 4 weeks in 100% of cases
-
Respiratory Failure requiring Mechanical Ventilation (25% of hospitalized cases)
- Onset within 1-2 weeks of symptoms
X. Symptoms
- Typically follows acute infectious illness
- Acute respiratory illness (fever, cough, Sore Throat)
- Acute gastrointestinal illness (Vomiting, Diarrhea)
- More likely to be associated with longer recovery and greater Disability (AMAN, AMSCAN subtypes)
- Progressive and ascending neurologic changes
- See signs below for more detailed description
- Tingling Paresthesias in distal extremities
- Proximal Muscle Weakness
- Myalgias (50% of cases)
XI. Signs
- Progressive, symmetric neurologic symptoms
- Classically starts in distal extremities and ascends
- However lesions are random and patients may present first with Cranial Nerve deficit
- Progresses proximally over days to weeks (peaking by 2 to 4 weeks)
- Paresthesias (tingling) in distal extremities
- Proximal Muscle Weakness
- Cranial Nerves may be affected
- Facial Muscles and eye movements may be affected (30-50% of cases)
- Ophthalmoplegia is rare except for in the Miller Fisher subtype
- Swallowing may be difficult
- Classically starts in distal extremities and ascends
- Progressive, symmetric proximal Muscle Weakness
- Legs are affected more than arms (due to longer Neurons more apt to accumulate damage)
- Often onset in the legs and ascends to involve arms
- Observe patient standing and walking if possible
- Severe weakness (10-30% of cases)
- Quadriparesis
- Respiratory arrest requiring Ventilator support
- Bulbar failure (e.g. Dysphagia)
- Loss of Deep Tendon Reflexes within first few days
- Variable sensory losses
- Most prevalent in AMSCAN subtype
-
Autonomic Dysfunction
- Hyperhidrosis
- Postural Hypotension and Blood Pressure fluctuation
- Tachycardia
- Urinary Retention
- Gastrointestinal pseudo-obstruction
XII. Diagnostics
- Cerebrospinal fluid (CSF)
- Albuminocytologic dissociation
- CSF Protein increased without increase in CSF White Blood Cells
- Increased CSF Protein >0.55 g/dl
- Increased by week 2 of symptoms in 90% of cases
- Normal CSF White Blood Cells Count (<10 cells/mm3)
- If increased, then consider other diagnosis
- Differential diagnosis if CSF WBCs increased
- Lyme Disease
- Cancer
- Human Immunodeficiency Virus (HIV Infection)
- Sarcoid Meningitis
- Albuminocytologic dissociation
-
Electromyogram (EMG)
- Slowing of Nerve Conduction to <60% of normal velocity within weeks of onset in 80% of cases
- Specific findings
- Absent H reflex
- Low to absent sensory Action Potential amplitudes
- F wave response prolonged
- Evaluate respiratory function in all suspected cases
XIII. Diagnosis: Major Criteria
- Bilateral, relatively symmetrical weakness or sensory deficit (typically with onset in legs)
- Decreased or absent Deep Tendon Reflexes
- Progressive and peaks within 4 weeks
- Not due to other cause
XIV. Differential Diagnosis: General
- See Acute Motor Weakness Causes
- See Symmetric Peripheral Neuropathy
- See Peripheral Neuropathy
- See Acute Motor Weakness Causes
- See Drug-Induced Polyneuropathy
- Brainstem Conditions
- Spinal Conditions
- Cord Compression (e.g. central spinal stenosis)
- Myelopathy
- Poliomyelitis
- Transverse Myelitis
- Muscular (and neuromuscular) Conditions
- Hypokalemia (includes periodic paralysis)
- Hypohosphatemia
- Myopathy
- Rhabdomyolysis
- Myasthenia Gravis
-
Polyneuropathy conditions
- Arsenic
- Botulism
- Chronic inflammatory demyelinating Polyneuropathy
- Diabetes Mellitus
- Diphtheria
- Lyme Disease
- Lymphoma
- n-hexane (exposure with Inhalant Abuse)
- Paraneoplastic conditions
- Porphyria
- Sarcoidosis
- Uremia
- Vasculitis
XV. Differential Diagnosis: Findings suggestive of alternative diagnosis
- Neurotoxic findings
- Porphyria
- Diphtheria
- Botulism
- Toxic Neuropathy
- Inhalant Abuse
- Occupational exposures
- Lead Poisoning
- Exam and lab findings not suggestive of Guillain-Barre
- Pure sensory deficits (sensory-only GBS is rare)
- Significant asymmetric neurologic symptoms or findings
- Well demarcated line of senory deficit
- Bowel or Bladder symptoms predominate
- CSF Leukocytosis (see diagnostics)
XVI. Management: Criteria for ICU admission (risk of Respiratory Failure)
-
Pulmonary Function Test abnormalities
- Vital Capacity < 20 ml/kg (or <60% of predicted)
- Peak inspiratory pressure <30 cm H2O
- Peak expiratory pressure <40 cm H2O
- Poor Swallowing
- Ineffective cough
- Aspiration Pneumonia
- Autonomic Dysfunction
- Increased Respiratory Rate
- Dyspnea
- Severe Muscle Weakness
- Unable to lift elbows above bed or flex arms
- Unable to lift head above bed
- Unable to stand
- Other predictors of Respiratory Failure and Mechanical Ventilation
- Rapid progression of symptoms over <7 days
- Arm weakness
- Elevated Liver Function Tests
- Bulbar palsy
XVII. Management: Indications for Intubation
- Consider when patient reports Dyspnea
-
Forced Vital Capacity <20 ml/kg
- Some criteria differentiate with bulbar weakness
- Vital Capacity 15-18 ml/kg with bulbar weakness
- Vital Capacity <15 ml/kg without bulbar weakness
- Pressure measurement criteria
- Maximal Inspiratory Pressure <30 cm H2O
- Maximal expiratory pressure <40 cm H2O
XVIII. Management: Supportive care
- Monitor for Respiratory Failure (25%)
- Incentive Spirometry
- Control Secretions
- Monitor for autonomic failure
- Arrhythmias
- Blood Pressure abnormalities
- Turn patient frequently (prevents Decubitus Ulcers)
- Subcutaneous Heparin (prevents Pulmonary Embolism)
- Fluid management (Observe for SIADH with low Sodium)
- Nutrition
- Monitor for infections (Urinary Tract Infection in 20%)
- Prevent exposure Keratitis
- Physical therapy reduces pain
- Gentle massage
- Range of motion
- Position changes
- Pain management (significant pain in affected Muscles)
- See physical therapy above
- NSAIDs
- Narcotics (use caution due to ileus)
- Carbamazepine (Tegretol)
- Gabapentin (Neurontin)
- Corticosteroids are no longer recommended
-
Ventilatory management
- See Endotracheal Intubation
- Rapid Sequence Intubation
- As with other neuromuscular disorders, avoid Succinylcholine for paralysis
- Acetylcholinesterase receptors are upregulated with increased risk for Hyperkalemia
- Neuromuscular Blockade risks ventricular Arrhythmia
- Indicators to start weaning
- Vital Capacity > 15 ml/kg (if no lung disease)
- Weaning
- First: Change Ventilator to IMV
- Later: lower the Respiratory Rate
XIX. Management: Specific Treatment
-
General
- Best efficacy if treatment given within first 2 weeks
- Both plasma exchange and IV-Ig are equally effective (choose one)
- Corticosteroids are not recommended
- No evidence of improved outcome
- Risk of delayed recovery
- Plasma Exchange (Plasmapheresis)
- Protocol
- Number of exchanges depends on severity (up to five exchanges total)
- Mild Guillain-Barre: 2 exchanges
- Moderate to severe Guillain-Barre: 4-5 exchanges
- Perform one exchange every other day for 4 to 10 days (2-5 exchanges)
- Best outcomes if started within first 7 days from onset
- Number of exchanges depends on severity (up to five exchanges total)
- Special Indications
- Pregnancy
- Renal Insufficiency
- IgA deficient
- Has not been studied in children
- Protocol
- IV Immunoglobulin
- Easier management with fewer complications than plasma exchange
- Dose
- Standard: IV-Ig 400 mg/kg daily for 5-7 days
- Alternative: IV-Ig 2g/kg total with divided dosing over 2 days
- Special Indications
- Children
- Poor venous access
- Autonomic instability
XX. Prognosis
- Full recovery within 6-12 months in 85% of cases
- Neurologic sequelae in up to 15-20%
- Foot Drop
- Hand intrinsic Muscle Weakness
- Sensory Ataxia
- Median hospitalization duration: 7 days
- Relapse rate <3-5%
- Mortality rate <3-5% overall
- Mortality approaches 20% in some studies if Mechanical Ventilation required
- Predictors of poor prognosis or longterm Disability
- Age over 60 years
- Rapidly progressive, severe disease
- EMG showing axonal loss
- Prolonged Mechanical Ventilation >1 month
- Absence of motor response
- Inability to walk at 14 days
- Trigger conditions associated with worse outcomes
- Preceding Diarrheal illness (often Campylobacter jejuni)
- Cytomegalovirus infection
XXI. Resources
- National Institute of Neurological Disorders and Stroke (NINDS)
- Guillain-Barre and Chronic Inflammatory Demyelinating Polyneuropathy Foundation International
XXII. References
- Gallagher in Marx (2002) Rosen's Emergency Med, p. 1510
- Shields in Goetz (2003) Neurology, p. 1085-90
- Weinstock et al. in Herbert (2015) EM:Rap 15(1): 7
- Alshekhlee (2008) Neurology 70(18): 1608-13 [PubMed]
- Cornblath (2009) Ann Nuerol 66(5): 569-70 [PubMed]
- Joseph (2002) Adolesc Med 13:487-94 [PubMed]
- Newswanger (2004) Am Fam Physician 69(10):2405-10 [PubMed]
- van Doorn (2008) Lancet Neurol 7(10): 939-50 [PubMed]
- Walling (2013) Am Fam Physician 87(3): 191-7 [PubMed]