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Subsections
Guillain-Barre Syndrome

Neurology

Guillain Barre Syndrome

Background

  1. Definition
    • Spectrum of autoimmune demyelinating disorders leading to acute inflammatory peripheral neuropathy
  2. Synopsis
    • Unknown trigger/etiology, often follows minor infection or weeks after surgery
    • Swine flu vaccination of 1976 may have caused rare cases
      • Regular and swine flu of today have not caused any cases
    • Guillain-Barré Syndrome (GBS) was originally a single disorder, but now considered several variant forms
    • Diagnosis
      • Clinical
      • NCS, EMG
      • CSF
    • Treatment
      • Respiratory support
      • Analgesics
      • Plasmapheresis
      • IVIG

Pathophysiology

  1. Mechanism
    • Post-infectious, immune-mediated disease (cellular and humoral immune mechanisms)
      • May be precipitated by systemic viral infection, immunizations, meds, pregnancy, surgery
      • Campylobacter jejuni has been implicated in many cases
      • Could be days to weeks after trigger
    • Infection induces antibody production that cross-react with gangliosides, glycolipids
      • Gangliosides, glycolipids in myelin of peripheral nervous system
      • Molecular mimicry implicated in process of auto-immune destruction of myelin
    • Lymphocytic infiltration of spinal roots, peripheral nerves
      • Then macrophages induce multifocal demyelination of nerves
    • Results in defective nerve impulse propagation leading to delay or absent conduction
      • Muscle weakness usually starts peripherally (i.e., toes, feet, legs)
      • Advances to flaccid paralysis as disease ascends nervous system
    • Severe disease can have axonal disruption/loss with sparing of myelin
      • Due to severe inflammation
    • Usually peak weakness in 10-14 days with recovery in weeks-months
      • Average time on ventilator (without treatment) is 50 days
  2. Subtypes
    • Acute inflammatory demyelinating polyneuropathy (AIDP)
      • Most common in USA
      • Preceded normally by bacterial/viral infection
      • 40% seropositive for C. jejuni
    • Acute motor axonal neuropathy (AMAN)
      • Prevalent in pediatric age group
      • Rapid, progressive, symmetric
      • Leads to respiratory failure
      • Up to 75% pos for Campylobacter
      • Wallerian-like degeneration, no lymphocytic inflammation
      • Hyper-reflexivity (in 1/3 cases) associated with anti-GM1 antibodies
    • Acute motor-sensory axonal neuropathy (AMSAN)
      • Typically adult, rapid, severe motor and sensory dysfunction
      • Marked muscle wasting
      • Preceded by C. jejuni diarrhea
      • Severe axonal degeneration of motor/sensory nerves
      • Little to no demyelination
    • Miller-Fisher Syndrome
      • Triad: ataxia, areflexia, acute onset ophthalmoplegia
      • Anti-ganglioside antibodies have high specificity/sensitivity for disease
      • Recovery in 4-12 wks
    • Acute panautonomic neuropathy
      • Very rare, involves sympathetic and parasympathetic
        • Postural hypotension, bowel/bladder retention, anhidrosis, decreased saliva/lacrimation
        • Pupillary abnormalities, dysrhythmias (increase mortality)
      • Recovery is gradual, usually incomplete
    • Pure sensory GBS
      • Symmetric, rapid onset sensory loss, areflexia
      • Demyelination of peripheral nerves
      • CSF: albuminocytologic dissociation
        • Increased CSF protein without increased cell count
    • Pharyngeal-cervical-brachial GBS
      • No lower limb involvement
      • Weakness of upper extremities, cervical, oropharyngeal, facial
  3. Etiology/Risk Factors
    • Bacterial/viral infection
      • Respiratory infection (most common)
      • Gastroenteritis
      • Pathogens
        • C. jejuni (common pathogen)
        • CMV, EBV, M. pneumoniae, VZV, HIV
        • H. influenzae, Borrelia, para-influenzae type 1, influenza B, adenovirus, HSV
    • Vaccinations
    • Medications
      • Streptokinase, isotretinoin, ACE-I, heavy metals, narcotics
    • Other autoimmune disease (i.e., SLE, sarcoidosis)
    • Systemic illnesses
      • Lymphoma, other tumors
    • Snakebite
    • Surgery
    • Trauma
    • Pregnancy
    • US military personnel
  4. Epidemiology
    • Incidence/Prevalence
      • Most common cause of paralytic disease worldwide
      • Incidence: 1-2 per 100,000 population annually
        • Male > female (ratio 1.78:1)
      • All ages affected
      • Bimodal peaks: young adults and elderly
    • Morbidity/Mortality
      • Good prognosis (85%)
      • Up to 20% sequelae
      • Worst prognosis aside from death is tetraplegia with incomplete recovery >18 months
      • 2-12% mortality rate due to complications
        • Usually in ventilator-dependent patients, due to respiratory failure, ARDS, sepsis
        • Worse in elderly, immunocompromised, pulmonary disease

Diagnostics

  1. History/Symptoms
    • Weakness
      • Ascending
      • Bilateral
      • Typically progressing over 1-4 days
      • Severity
        • Ranges from mild weakness to complete tetraplegia with respiratory failure due to ventilation muscle weakness/failure
        • Mild form
          • Difficulty with gait and use of upper extremities
        • Moderate form
          • Assistance needed to walk
        • Severe form
          • Typically maximal 10-14 days after onset
          • Ascending paralysis
          • May involve diaphragm and cranial nerves
          • Autonomic instability
          • Urinary retention, constipation
          • CNS effects including hallucinations, psychosis
    • Other symptoms
      • Cranial nerves may be involved
        • Pupillary disturbances, ophthalmoplegia
        • Difficulty swallowing, speaking
        • Facial droop
      • Mild-severe pain following progression of GBS
        • Aching, throbbing, shoulder girdle, back, buttocks, thighs
        • Burning, tingling, shocking pain legs > arms
      • Autonomic changes (sympathetic and parasympathetic)
      • Shortness of breath, dyspnea with exertion
    • Recent history of:
      • Infection: typically viral GI or URI
      • Immunizations
      • Malignancies
      • Pregnancy
    • 2-4 wks after illness:
      • Weakness, numbness, tingling of fingers, toes
      • Ascending progression, symmetrical
      • Lower limbs usually first
  2. Physical Exam/Signs
    • General, Vitals: variable, but mild-severe distress, possible low BP
    • Neuro exam (sympathetic and parasympathetic)
      • HEENT: cranial nerve involvement
        • Facial droop, diplopia, decreased vision, ophthalmoparesis, ptosis, pupillary abnormalities, papilledema
        • Slurred speech, dysarthria, dysphagia
      • Cardiovascular (BP lability)
        • Tachy/bradycardia, paroxysmal HTN, orthostatic hypotension, arrhythmias
        • Flushing (face)
      • Pulmonary/Chest
        • Respiratory failure (ventilation difficulty), dyspnea on exertion, tachypnea
        • Poor inspiratory effort, diminished breath sounds
      • Abd/GI/GU
        • Absent bowel sounds, suprapubic tenderness/fullness
      • Extremities
        • Weakness, loss of sensation
        • Hyporeflexia or loss of reflexes
        • Symmetric, ascending progression, usually legs first, then arms
        • Absent Babinski, hypotonia (severe disease)
      • Skin flushing (especially face) due to cardiovascular lability (sympathetic/parasympathetic dysfunction)
  3. Labs/Tests
    • Diagnosis based on clinical exam
      • Labs/tests to confirm or rule out other disease
    • CBC +Diff, chemistry, CPK, LFTs, electrolytes (rule out other disease)
    • Serology
      • CMV, EBV, HSV, HIV, M. pneumoniae, C. jejuni
    • Peripheral neuropathy work-up
      • Thyroid panel, rheumatology profiles
      • Vitamin levels, heavy metals levels, serum protein levels
      • ESR, hemoglobin A1C
    • Stool culture (C. jejuni)
  4. Imaging
    • CT/MRI
      • Brain, spine, legs, arms (rule out other disease, trauma, myelopathy)
  5. Other Tests/Criteria
    • Pulmonary function tests
      • To assess and monitor pulmonary function
    • Nerve conduction studies (NCS)
      • Characteristic demyelination signs (i.e., slow conduction, prolonged distal latency)
      • Changes may not appear for weeks
    • EMG: abnormal
    • ECG/echocardiography
      • Rule out heart disease; check heart condition
    • Lumbar puncture (LP)
      • CSF
        • Opening pressure: normal or elevated
        • Protein: high (100-1,000 mg/dL)
        • WBCs: normal
        • Glucose: normal
        • Culture: negative
      • CSF may be normal during first few days
    • Criteria necessary for clinical diagnosis:
      • Other etiologies for flaccid weakness have been ruled out
      • Diminished or absent reflexes
      • Symmetric weakness from the onset of the symptoms
      • Subacutely developing flaccid paralysis over < 4 weeks
  6. Differential Diagnosis

Treatment

  1. Initial/Prep/Goals
    • ABCs
      • Ensure adequate ventilatory ability
    • Monitor:
      • Blood gases
      • Pulmonary function
    • Supportive management
    • Intubate if:
      • Vital capacity <15 mg/kg
      • Difficulty breathing, swallowing or speaking
      • PaO2 < 70 (room air)
      • Aspiration
      • Note:
    • Immunotherapy
      • Plasmapheresis
      • IVIG
      • Combining the two treatments is not recommended
        • No greater effect than either treatment alone
    • ICU transfer indications:
      • Autonomic dysfunction
      • Bulbar dysfunction
      • Inability to ambulate
      • Vital capacity (initial): < 20 mL/kg
      • Vital capacity reduction > 30%
      • Plasmapheresis
      • ≥ 4 of the following:
        • Unable to lift head
        • Unable to stand
        • Unable to lift elbows
        • Elevate liver enzymes
        • Time from symptom onset to hospital: < 7 days
  2. Medical/Pharmaceutical
    • Most cases managed in ICU
    • Analgesia
    • IVIG
      • May be helpful if <14 days after onset of symptoms
      • Similar efficacy to plasmapheresis
    • Anticoagulants
    • Inpatient physical therapy may be necessary
    • Steroids
      • Not recommended for the treatment of GBS
      • May prolong the recovery
  3. Surgical/Procedural
    • Plasmapheresis
      • Most effective when done < 7 days after onset of symptoms
      • Similar efficacy to IVIG
      • Monitor/treat autonomic dysfunctions (especially arrhythmias)
    • Pacemaker
      • May be indicated for severe bradycardia
  4. Complications
    • Residual weakness, loss of sensation
    • Respiratory compromise
    • Pulmonary embolism
    • Paralytic ileus
    • Bradycardia/asystole
    • DVT

Disposition

  1. Admission Criteria
    • Admit all suspected cases
    • Consider transfer to ICU
  2. Consult(s)
    • Occupational/recreational/speech therapy may be needed
  3. Discharge/Follow-up instructions
    • Long-term follow-up care with therapist/primary healthcare provider(s)

References

  1. Yuki N, Hartung HP. Guillian-Barré Syndrome. N Engl J Med June 14, 2012; 366: 2294-304
  2. Walgard C, Lingsma HF, Ruts L et al. Early recognition of poor prognosis in Guillian-Barré syndrome. Neurology 2011; 76: 968-975
  3. Khan F, Ng L, Amatya B, Brand C, Turner-Stokes L. Multidisciplinary care for Guillian-Barré. Cochrane Database of Systematic Reviews 2010; Issue 10. Art. No: CD008505
  4. Jacobs BC, Koga M, et al. Subclass IgG to motor gangliosides related to infection and clinical course in Guillain-Barré syndrome. Journ Neuroimmun. February 2008;194(1-2):181-90
  5. Nelson L, Gormley R, Riddle MS, Tribble DR, Porter CK. The epidemiology of Guillain-Barré Syndrome in U.S. military personnel: a case-control study. BMC Res Notes. Aug 26 2009;2:171
  6. Kang JH, Sheu JJ, Lin HC. Increased risk of Guillain-Barré Syndrome following recent herpes zoster: a population-based study across Taiwan. Clin Infect Dis. Sep 1 2010;51(5):525-30
  7. Kalra V, Chaudhry R, Dua T, Dhawan B, Sahu JK, Mridula B. Association of Campylobacter jejuni infection with childhood Guillain-Barré syndrome: a case-control study. J Child Neurol. Jun 2009;24(6):664-8
  8. Kuitwaard K, Bos-Eyssen ME, Blomkwist-Markens PH, van Doorn PA. Recurrences, vaccinations and long-term symptoms in GBS and CIDP. Journ Peripheral Nervous System, Dec 2009;14(4):310-5
  9. Baravelli M, Fantoni C, Rossi A, et al. Guillain-Barré syndrome as a neurological complication of infective endocarditis. Is it really so rare and how often do we recognise it? Int J Cardiol. March 20, 2009;133(1):104-105
  10. Fokke C, van den Berg B, Drenthen J, et al. Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria. Brain. Jan 1, 2014;137(1):33-43
  11. In: Tintinalli JE, Stapczynski JS, Ma OJ, et al; (eds). Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 8th ed, McGraw-Hill Education, 2016;Chapter 172
  12. Guillain-Barre Syndrome. StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK532254/. [Accessed January 2025]

Contributor(s)

  1. Ho, Nghia, MD
  2. Muench, Diane, RN, MBA, OCN
  3. Ballarin, Daniel, MD

Updated/Reviewed: January 2025