Demyelinating

Guillain Barre Syndrome

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Guillain Barre Syndrome, Guillain-Barre Syndrome, Landry-Guillain-Barre Syndrome, Guillain-Barre-Strohl Syndrome, Acute Inflammatory Demyelinating Polyradiculoneuropathy, Acute Motor Axonal Neuropathy, Acute Motor Sensory Axonal Neuropathy, Miller Fisher Syndrome

  • Definition
  1. Progressive, idiopathic, symmetrical weakness and loss of Deep Tendon Reflexes reaching maximal intensity within 4 weeks
  • Epidemiology
  1. Incidence
    1. Annual Incidence: 1-3 cases per 100,000
    2. Incidence increases with advancing age
  2. Gender
    1. Male to female ratio: 3 to 2
  • Precautions
  1. Presentation may have subtle, non-specific findings early in the course
    1. Focal Paresthesias
    2. Perception of weakness without motor weakness on exam
    3. Deep Tendon Reflexes may initially be preserved, and may appear to be asymmetric
  • Pathophysiology
  1. Inflammatory Neuropathy with cross reactivity between antibodies to infectious agents and neural antigens
  2. Lipooligosaccharides in Bacterial cell wall resemble gangliosides
  3. Anti-ganglioside antibodies form in response to acute infections (e.g. Diarrhea with Campylobacter jejuni)
  • Types
  • Most Common Subtypes
  1. Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)
    1. Most common subtype in the United States (90% of cases)
    2. Multifocal peripheral demyelination with slow remyelination
      1. Presents with progressive symmetrical weakness and hyporeflexia
      2. Symptoms start in legs in 90% of cases
      3. Myelin predominantly injured
  2. Acute Motor Axonal Neuropathy (AMAN)
    1. Accounts for 5-10% of Guillain-Barre Syndrome cases in U.S.
    2. Anti-ganglioside antibodies (GM1, GD1a, GalNAc-GD1a, GD1b) bind in peripheral Motor Nerve axons
    3. Most associated with Campylobacter jejuni infection (esp. younger patients, summer, China and Japan)
    4. Pure motor Neuropathy
    5. No demyelination (contrast with AIDP)
    6. Nodes of Ranvier predominantly injured
  3. Acute Motor Sensory Axonal Neuropathy (AMSCAN)
    1. Similar to AMAN subtype, but sensory Neuropathy predominates
  • Types
  • Rare Subtypes
  1. Miller Fisher Syndrome (3% of cases)
    1. Anti-ganglioside antibodies (GQ1b, GD3, GT1a)
    2. Bilateral Ophthalmoplegia, Ataxia and areflexia
    3. Facial or bulbar weakness (50% of cases)
    4. Trunk and extremity weakness (50% of cases)
  2. Acute Panautonomic Neuropathy (rarest)
    1. Autonomic symptoms (cardiovascular and visual)
    2. Sensory loss
    3. Slow, often incomplete recovery
  • Risk Factors
  1. Acute infection precedes Guillain-Barre in 66% of cases
    1. Campylobacter jejuni (most common)
      1. Guillain-Barre occurs in one in 1000 patient infected with Campylobacter jejuni
    2. Epstein-Barr Virus (Mononucleosis)
      1. Associated with milder forms of Guillain-Barre
    3. Mycoplasma pneumoniae
    4. HaemophilusInfluenzae
    5. Cytomegalovirus
    6. HIV Infection
    7. Varicella Zoster Virus
    8. Vector-Borne Infections (Mosquito borne)
      1. West Nile Virus
      2. Zika Virus
  2. Vaccinations are associated with no significant increased risk
    1. H1N1 Influenza Vaccine was associated with a risk of 1-2 cases per 1 Million
    2. Tetanus Vaccine and hepatitis Vaccines also have minimal increased risk
    3. De Wals (2012) JAMA 308(2): 175-81 [PubMed]
  • Course
  1. Peak timing
    1. Peaks by 2 weeks in 50% of cases
    2. Peaks by 3 weeks in 80% of cases
    3. Peaks by 4 weeks in 100% of cases
  2. Respiratory Failure requiring Mechanical Ventilation (25% of hospitalized cases)
    1. Onset within 1-2 weeks of symptoms
  • Symptoms
  1. Typically follows acute infectious illness
    1. Acute respiratory illness (fever, cough, Sore Throat)
    2. Acute gastrointestinal illness (Vomiting, Diarrhea)
      1. More likely to be associated with longer recovery and greater Disability (AMAN, AMSCAN subtypes)
  2. Progressive and ascending neurologic changes
    1. See signs below for more detailed description
    2. Tingling Paresthesias in distal extremities
    3. Proximal Muscle Weakness
  3. Myalgias (50% of cases)
    1. Deep, often severe aching pain in weak muscles
    2. Worse with movement, and at night
    3. Distribution (most common sites)
      1. Shoulder
      2. Back
      3. Posterior thighs
  • Signs
  1. Progressive, symmetric neurologic symptoms
    1. Classically starts in distal extremities and ascends
      1. However lesions are random and patients may present first with Cranial Nerve deficit
    2. Progresses proximally over days to weeks (peaking by 2 to 4 weeks)
      1. Paresthesias (tingling) in distal extremities
      2. Proximal Muscle Weakness
      3. Cranial Nerves may be affected
        1. Facial muscles and eye movements may be affected (30-50% of cases)
        2. Ophthalmoplegia is rare except for in the Miller Fisher subtype
        3. Swallowing may be difficult
  2. Progressive, symmetric proximal Muscle Weakness
    1. Legs are affected more than arms (due to longer Neurons more apt to accumulate damage)
    2. Often onset in the legs and ascends to involve arms
    3. Observe patient standing and walking if possible
  3. Severe weakness (10-30% of cases)
    1. Quadriparesis
    2. Respiratory arrest requiring Ventilator support
    3. Bulbar failure (e.g. Dysphagia)
  4. Loss of Deep Tendon Reflexes within first few days
  5. Variable sensory losses
    1. Most prevalent in AMSCAN subtype
  6. Autonomic Dysfunction
    1. Hyperhidrosis
    2. Postural Hypotension and Blood Pressure fluctuation
    3. Tachycardia
    4. Urinary Retention
    5. Gastrointestinal pseudo-obstruction
  • Diagnostics
  1. Cerebrospinal fluid (CSF)
    1. Albuminocytologic dissociation
      1. CSF Protein increased without increase in CSF White Blood Cells
    2. Increased CSF Protein >0.55 g/dl
      1. Increased by week 2 of symptoms in 90% of cases
    3. Normal CSF White Blood Cells Count (<10 cells/mm3)
      1. If increased, then consider other diagnosis
      2. Differential diagnosis if CSF WBCs increased
        1. Lyme Disease
        2. Cancer
        3. Human Immunodeficiency Virus (HIV Infection)
        4. Sarcoid Meningitis
  2. Electromyogram (EMG)
    1. Slowing of nerve conduction to <60% of normal velocity within weeks of onset in 80% of cases
    2. Specific findings
      1. Absent H reflex
      2. Low to absent sensory action potential amplitudes
      3. F wave response prolonged
  3. Evaluate respiratory function in all suspected cases
    1. Pulmonary Function Testing
    2. Arterial Blood Gas
  • Diagnosis
  • Major Criteria
  1. Bilateral, relatively symmetrical weakness or sensory deficit (typically with onset in legs)
  2. Decreased or absent Deep Tendon Reflexes
  3. Progressive and peaks within 4 weeks
  4. Not due to other cause
  • Differential Diagnosis
  • General
  1. See Acute Motor Weakness Causes
  2. See Symmetric Peripheral Neuropathy
  3. See Peripheral Neuropathy
  4. See Acute Motor Weakness Causes
  5. See Drug-Induced Polyneuropathy
  6. Brainstem Conditions
    1. Cerebrovascular Accident
    2. Encephalitis
    3. Meningitis
  7. Spinal Conditions
    1. Cord Compression (e.g. central spinal stenosis)
    2. Myelopathy
    3. Poliomyelitis
    4. Transverse Myelitis
  8. Muscular (and neuromuscular) Conditions
    1. Hypokalemia (includes periodic paralysis)
    2. Hypohosphatemia
    3. Myopathy
    4. Rhabdomyolysis
    5. Myasthenia Gravis
  9. Polyneuropathy conditions
    1. Arsenic
    2. Botulism
    3. Chronic inflammatory demyelinating Polyneuropathy
    4. Diabetes Mellitus
    5. Diphtheria
    6. Lyme Disease
    7. Lymphoma
    8. n-hexane (exposure with Inhalant Abuse)
    9. Paraneoplastic conditions
    10. Porphyria
    11. Sarcoidosis
    12. Uremia
    13. Vasculitis
  • Differential Diagnosis
  • Findings suggestive of alternative diagnosis
  1. Neurotoxic findings
    1. Porphyria
    2. Diphtheria
    3. Botulism
    4. Toxic Neuropathy
    5. Inhalant Abuse
    6. Occupational exposures
    7. Lead Poisoning
  2. Exam and lab findings not suggestive of Guillain-Barre
    1. Pure sensory deficits (sensory-only GBS is rare)
    2. Significant asymmetric neurologic symptoms or findings
    3. Well demarcated line of senory deficit
    4. Bowel or Bladder symptoms predominate
    5. CSF Leukocytosis (see diagnostics)
  1. Pulmonary Function Test abnormalities
    1. Vital Capacity < 20 ml/kg (or <60% of predicted)
    2. Peak inspiratory pressure <30 cm H2O
    3. Peak expiratory pressure <40 cm H2O
  2. Poor swallowing
  3. Ineffective cough
  4. Aspiration Pneumonia
  5. Autonomic Dysfunction
  6. Increased Respiratory Rate
  7. Dyspnea
  8. Severe Muscle Weakness
    1. Unable to lift elbows above bed or flex arms
    2. Unable to lift head above bed
    3. Unable to stand
  9. Other predictors of Respiratory Failure and Mechanical Ventilation
    1. Rapid progression of symptoms over <7 days
    2. Arm weakness
    3. Elevated Liver Function Tests
    4. Bulbar palsy
  • Management
  • Indications for Intubation
  1. Consider when patient reports Dyspnea
  2. Forced Vital Capacity <20 ml/kg
    1. Some criteria differentiate with bulbar weakness
    2. Vital Capacity 15-18 ml/kg with bulbar weakness
    3. Vital Capacity <15 ml/kg without bulbar weakness
  3. Pressure measurement criteria
    1. Maximal inspiratory pressure <30 cm H2O
    2. Maximal expiratory pressure <40 cm H2O
  • Management
  • Supportive care
  1. Monitor for Respiratory Failure (25%)
    1. Incentive Spirometry
    2. Control Secretions
  2. Monitor for autonomic failure
    1. Arrhythmias
    2. Blood Pressure abnormalities
  3. Turn patient frequently (prevents Decubitus Ulcers)
  4. Subcutaneous Heparin (prevents Pulmonary Embolism)
  5. Fluid management (Observe for SIADH with low Sodium)
  6. Nutrition
  7. Monitor for infections (Urinary Tract Infection in 20%)
  8. Prevent exposure Keratitis
  9. Physical therapy reduces pain
    1. Gentle massage
    2. Range of motion
    3. Position changes
  10. Pain management (significant pain in affected muscles)
    1. See physical therapy above
    2. NSAIDs
    3. Narcotics (use caution due to ileus)
    4. Carbamazepine (Tegretol)
    5. Gabapentin (Neurontin)
    6. Corticosteroids are no longer recommended
      1. Van Der Meche (1992) N Engl J Med 326:1123-9 [PubMed]
  11. Ventilatory management
    1. Indicators to start weaning
      1. Vital Capacity > 15 ml/kg (if no lung disease)
    2. Weaning
      1. First: Change to IMV
      2. Later: lower the Respiratory Rate
  • Management
  • Specific Treatment
  1. General
    1. Best efficacy if treatment given within first 2 weeks
    2. Both plasma exchange and IV-Ig are equally effective (choose one)
    3. Corticosteroids are not recommended
      1. No evidence of improved outcome
      2. Risk of delayed recovery
  2. Plasma Exchange (Plasmapheresis)
    1. Protocol
      1. Number of exchanges depends on severity (up to five exchanges total)
        1. Mild Guillain-Barre: 2 exchanges
        2. Moderate to severe Guillain-Barre: 4-5 exchanges
      2. Perform one exchange every other day for 4 to 10 days (2-5 exchanges)
      3. Best outcomes if started within first 7 days from onset
    2. Special Indications
      1. Pregnancy
      2. Renal Insufficiency
      3. IgA deficient
      4. Has not been studied in children
  3. IV Immunoglobulin
    1. Easier management with fewer complications than plasma exchange
    2. Dose
      1. Standard: IV-Ig 400 mg/kg daily for 5-7 days
      2. Alternative: IV-Ig 2g/kg total with divided dosing over 2 days
    3. Special Indications
      1. Children
      2. Poor venous access
      3. Autonomic instability
  • Prognosis
  1. Full recovery within 6-12 months in 85% of cases
  2. Neurologic sequelae in up to 15-20%
    1. Foot drop
    2. Hand intrinsic Muscle Weakness
    3. Sensory Ataxia
  3. Median hospitalization duration: 7 days
  4. Relapse rate <3-5%
  5. Mortality rate <3-5% overall
    1. Mortality approaches 20% in some studies if Mechanical Ventilation required
  6. Predictors of poor prognosis or longterm Disability
    1. Age over 60 years
    2. Rapidly progressive, severe disease
    3. EMG showing axonal loss
    4. Prolonged Mechanical Ventilation >1 month
    5. Absence of motor response
    6. Inability to walk at 14 days
  7. Trigger conditions associated with worse outcomes
    1. Preceding Diarrheal illness (often Campylobacter jejuni)
    2. Cytomegalovirus infection
  • Resources
  1. National Institute of Neurological Disorders and Stroke (NINDS)
    1. http://www.ninds.nih.gov/disorders/gbs/gbs.htm
  2. Guillain-Barre and Chronic Inflammatory Demyelinating Polyneuropathy Foundation International
    1. http://www.gbs-cidp.org/