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Subsections
Guillain-Barre Syndrome

Brainstem/Cord Disease

Guillain-Barre Syndrome

Background

  1. Definitions
    • Guillain-Barre Syndrome (GBS)
      • Life-threatening autoimmune disorder
      • Immune system attacks part of nervous system
      • Causes nerve inflammation leading to muscle weakness
    • Also known as
      • Landry-Guillain-Barre syndrome
      • Acute idiopathic polyneuritis
      • Infectious polyneuritis
      • Acute inflammatory polyneuropathy
      • Acute inflammatory demyelinating polyneuropathy (AIDP)
  2. General Information
    • GBS often follows minor respiratory or gastrointestinal infection
    • Usually presents after the signs of original infection have disappeared
    • Immune system attacks nerve coverings (myelin sheath) causing demyelination
      • Results in nerve signal slowing
    • In severe cases, damage can be more extensive, resulting in complete loss of nerve function
    • Subtypes
      • Acute inflammatory demyelinating polyradiculopathy (AIDP)
      • Acute motor axonal neuropathy (AMAN)
      • Acute motor sensory axonal neuropathy (AMSAN)
      • Miller-Fisher syndrome
      • Acute panautonomic neuropathy (rarest of subtypes)

Pathophysiology

  1. Pathology of Disease
    • Guillain-Barre Syndrome (GBS) primarily involves peripheral nervous system
    • Autoantibodies bind to gangliosides of nerve tissue and activate immune response; leads to inflammatory axon infiltration and secondary myelin impairment
    • Pathologic findings include lymphocyte infiltration of spinal roots and peripheral nerves with subsequent macrophage-mediated stripping of myelin
  2. Epidemiology
    • Incidence/Prevalence
      • Incidence ranges from 0.62 cases/100,000 person-years (ages 0-9) to 2.66 cases/100,000 person-years (ages 80-89) in North America and Europe
      • Relative risk for males 1.78 compared to females
      • Incidence thought to be higher in parts of Asia
    • Morbidity/Mortality
      • In one study of 76 patients admitted to ICU with confirmed GBS
      • ICU stay averaged 21 days
      • Mechanical ventilation (MV) required in 78% (median duration 28 days)
      • 2/3 suffered at least one major complication, most commonly pneumonia (54%)
      • Morbidity strongly associated with mechanical ventilation and male sex
      • Over an average 3 years follow-up, recovery of independent ambulation seen in 75% of patients
        • Time to ambulate was median of 198 days; although seen as late as 10 years after onset
      • Prolonged mechanical ventilation and severe axonal loss did not preclude favorable recovery
      • Slower recovery associated with ICU complications, prolonged mechanical ventilation, and early axonal abnormalities
      • Mortality occurred in 6.5% of patients
  3. Risk Factors
    • Risk factors for GBS may include
      • Age: Increased incidence in late adolescence/young adult and elderly
      • Men > Women
      • Recent gastrointestinal/respiratory infection by viruses/bacteria within 6 weeks
      • Usual pathogens include
        • Epstein-Barr virus
        • Mycoplasma pneumoniae
        • Campylobacter jejuni
        • Cytomegalovirus
    • Recent vaccination (especially influenza and meningococcal)
      • Swine flu vaccine, given from 1976-1977, linked to excess GBS cases
      • Since that time, influenza virus vaccines associated with only marginally increased GBS risk
    • Recent surgery
    • History of lymphoma, lupus, or AIDS

Diagnostics

  1. History/Symptoms
    • History benign respiratory/abdominal infection
    • Ascending, symmetrical motor weakness
    • Cranial nerve involvement
      • Facial droops, dysphagia, ophthalmoplegia, diplopia
    • Sensory disturbances
      • Paresthesias, numbness
    • Pain/Dysesthesias
      • Most severe in shoulder girdle area, back, thighs
      • Burning, shock-like sensations more prevalent in LE vs UE
  2. Physical Exam/Signs
    • Required for diagnosis
      • Progressive motor weakness in both LE and UE with areflexia
        • DTR absent or reduced early in disease course
        • Pathologic reflexes such as Babinski are absent
        • Hypotonia
    • Dysautonomia frequently seen
      • Hypertension
      • Orthostatic hypotension
      • Pupillary dysfunction
      • Sweating abnormalities
      • Sinus tachycardia
    • Respiratory
      • GBS most common peripheral neuropathy causing respiratory paralysis
      • Mechanical ventilation usually required by 1/3 of patients
      • 20% mortality rate for ventilated patients
  3. Diagnostic Testing
    • Lumbar puncture (LP) recommended
      • Most patients will have elevated protein (> 400 mg/L) with normal cell count
      • May need serial LP draws
      • Normal CSF protein level does not rule-out GBS
      • Consider other diagnosis if CSF leukocytosis exceeds 50 cells/µL
      • CSF pleocytosis well recognized in HIV associated GBS
    • Nerve Conduction Studies
      • Nerve conduction slowing
      • Prolonged distal latencies
      • Prolonged or absent F waves
      • Conduction block or dispersion
      • Prolonged distal compound muscle action potential (CMAP; early GBS)
    • Electromyogram (EMG) evaluates muscle activity and indicate signs of slow or blocked nerve conduction
    • Biopsy in unclear cases
    • Electrocardiogram (ECG) to rule out other sources of cardiovascular dysfunction
  4. Laboratory Evaluation
    • CBC, BMP, ESR, CRP, urine tests
    • HIV test done in patients who have risk factors for HIV or CSF pleocytosis
    • Serologic tests for antibodies are not clinically available with 1 exception:
      • Serum IgG antibodies to GQ1b for diagnosis of Miller-Fisher Syndrome
    • CSF findings
      • Often normal when symptoms present for < 48 hours
      • By end of the first week, protein level usually elevated
        • CSF protein 1–10 g/L (100–1000 mg/dL) without accompanying pleocytosis after first week
      • Occasionally, transient mild increase in CSF white cell count (10–100/µL) occurs early in the GBS course
      • Sustained CSF pleocytosis suggests alternative diagnosis (e.g., viral myelitis) or concurrent diagnosis (e.g., unrecognized HIV infection)
  5. Diagnostic Imaging
    • Not indicated unless needed to rule-out other diagnoses
      • X-rays, CT or MRI scans
  6. Other Studies
    • Electrodiagnostic features
      • AIDP = findings of demyelination (consider Miller-Fisher syndrome)
      • AMAN = findings of acute motor axonal neuropathy (normal sensory nerves)
      • AMSAN = similar to AMAN except affects sensory nerves and roots (Wallerian-like degeneration of myelinated motor and sensory fibers)
      • Miller-Fisher syndrome = reduced or absent sensory nerve action potentials; demyelination and inflammation of cranial nerve III and VI, spinal ganglia and peripheral nerves
      • Acute panautonomic neuropathy – cardiovascular involvement common
      • Abnormalities mild or absent in early stages and lag behind the clinical evolution
      • In cases with demyelination, usual features include: prolonged distal latencies, conduction velocity slowing, evidence of conduction block, and temporal dispersion of compound action potential
      • In cases with primary axonal pathology, principal finding is reduced amplitude of compound action potentials
        • Conduction slowing and of distal latency prolongation are absent
      • Electrodiagnostic testing can be helpful in rare instances when muscular (e.g., polymyositis) or neuromuscular junction (e.g., myasthenia gravis) disorder must be ruled out
  7. Diagnostic Criteria
    • Features required for diagnosis
      • Progressive weakness in both arms and legs; areflexia
    • Features strongly supporting diagnosis
      • Progression of symptoms over days, up to four weeks
      • Relative symptom symmetry
      • Mild sensory signs/symptoms
      • Cranial nerve involvement, especially bilateral facial muscle weakness
      • Recovery beginning two to four weeks after progression ceases
      • Autonomic dysfunction
      • Absence of fever at onset
      • High concentration of protein in cerebrospinal fluid, with < 10 cells/mm3
      • Typical electrodiagnostic features
    • Features excluding diagnosis
      • Diagnosis of botulism, myasthenia, poliomyelitis or toxic neuropathy
      • Abnormal porphyrin metabolism
      • Recent diphtheria
      • Purely sensory syndrome, without weakness
  8. Differential Diagnosis
    • Key Differential Diagnoses (when neuropathy identified)
      • Infection
      • Inflammatory (neurosarcoidosis)
      • Paraneoplastic (chronic)
      • Malignant (infiltration of roots)
      • Vasculitis (mononeuropathy)
      • Metabolic (vitamin B1 deficiency)
    • Extensive Differential Diagnoses
      • Basilar artery occlusion
        • Asymmetric limb paresis
      • Botulism
        • Descending paralysis
      • Heavy metal intoxication
        • Confusion, psychosis, organic brain syndrome
      • Hypophosphatemia
        • Irritable, apprehensive, hyperventilation, normal CSF
      • Metabolic myopathies
        • Cerebral and cerebellar symptoms
      • Myasthenia gravis
        • Weakness and fatigue that improves with rest
      • Neoplastic meningitis
        • Asymmetric spastic paralysis
      • Neurotoxic fish poisoning
      • Spontaneous recovery within 24 hours
      • Poliomyelitis
        • Purely motor disorder with meningitis
      • Polymyositis
        • Chronic, affects proximal limb muscles
      • Spinal cord compression
        • Asymmetric
      • Tick paralysis
        • Sensory changes absent, normal cerebrospinal fluid
      • Transverse myelitis
        • Abrupt bilateral leg weakness, ascending sensory

Therapeutics

  1. Acute therapy
  2. Supportive care
    • Respiratory
      • Increased risk of intubation
        • Time of onset to admission less than seven days
        • Inability to cough
        • Inability to stand
        • Inability to lift the elbows
        • Inability to lift the head
        • Elevate liver enzymes
      • Indications for intubation
        • FVC < 20 mL/kg
        • Maximum inspiratory pressure < 30 cmH2O
        • Maximum expiratory pressure < 40 cmH2O
    • Autonomic dysfunction
    • Cardiac dysrhythmias
      • Requires monitoring
      • ACLS protocols
    • GI
      • Ileus
    • Urinary tract
      • Urinary retention
    • DVT prophylaxis

Follow-Up

  1. Outpatient follow-up after discharge
  2. Multidisciplinary team approach may be necessary depending on extent of neurological damage
    • Neurology
    • Pulmonology
    • Physical therapy
    • Occupational therapy
  3. Primary care provider to coordinate care
    • Follow-up within 2 weeks after acute syndrome to evaluate for relapse
      • Consider repeat intravenous immunoglobulin or plasma exchange
    • Follow-up every 4 - 6 weeks for 6 months, then to every 6 months for 1 year, then once yearly
    • Patients should be educated to contact provider with
      • Any new or worsening neurologic symptoms
        • Weakness
        • Paresthesia
        • Facial weakness
        • Difficulty swallowing or breathing
        • Change in bladder function

Prognosis

  1. Symptoms reach clinical nadir between 2 to 4 weeks
  2. Some patients have persistent minor weakness, areflexia, and paresthesia.
  3. Walking returns in 2-3 months
  4. One year after treatment
    • Full recovery of motor strength 60%,
    • Severe motor dysfunction 14%
    • Prolonged course and incomplete recover 5-10%
  5. Approximately 7 to 20% of patients have permanent neurologic sequelae
    • Bilateral foot drop
    • Intrinsic hand muscle wasting
    • Sensory ataxia
    • Dysesthesia
  6. Mortality 3-7%
    • Poor prognosis
      • Rapid onset
      • Initial presentation of severe muscle weakness
      • Respiratory failure and need for intubation

Prevention

  1. No definite preventive recommendations for GBS
  2. Other immunizations not recommended during acute disease phase and are not suggested for period of ≥ 1 year after onset

References

  1. Hughes RA, Raphael JC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2009;(1):CD002063.
  2. Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: immunotherapy for Guillain-Barre syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003;61(6):736-740.
  3. Shy ME. Peripheral neuropathies. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier;2007:chap 446
  4. Pithadia AB, Kakadia N. Guillain-Barre Syndrome. Pharmalogical Reports 2010;62:220-232.
  5. Sejvar J, Baughman A, Wise M, Morgan O. Population Incidence of Guillain-Barre Syndrome: A Systematic Review and Meta-Analysis. Neuroepidemiology 2011;36:123-133.
  6. Vucic S, Kiernan MC, Cornblath DR. Guilain-Barre: an update. J Clinical Neuroscience. 2009;16(6):733-741.
  7. Rajat Dhar, Larry Stitt, Angelika F. Hahn; The morbidity and outcome of patients with Guillain–Barré syndrome admitted to the intensive care unit; Journal of the Neurological Sciences, Volume 264, Issues 1-2, 15 January 2008, Pages 121-128
  8. Newswanger, DL; CR Warren; Guillain-Barré Syndrome. Am Fam Physician. 2004 May 15;69(10):2405-2410.
  9. Hsieh M.D., David T; Bernard L Maria MD; Guillain-Barre Syndrome in Children, Wilford Hall Medical Center and the Uniformed Services University of the Health Sciences. Originally released November 15, 1999; Last updated April 5, 2011
  10. Pritchard J. Guillain-Barre Syndrome. Clinical Medicine 2010; 10(4):399-401
  11. Winer JB, S Jacob; Guillain-Barre syndrome. Best Practice, BMJ, Apr 14, 2011
  12. Kehoe M. Guillain-Barré syndrome--a patient guide and nursing resource. Axone. 2001 Jun;22(4):16-24.
  13. Sharshar T, Chevret S, Bourdain F, et al. Early predictors of mechanical ventilation in Guillain-Barré syndrome. Crit Care Med. 2003. 31(1):278-83
  14. GBS Prognostic Tools. https://gbstools.erasmusmc.nl/prognosis-tool/0/0 Updated 2020. Accessed 20Mar20
  15. Lawn ND, Fletcher DD, Henderson RD, et al. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol. 2001. 58(6):893-8.
  16. Walgaard C, Lingsma HF, Ruts L, et al. Prediction of respiratory insufficiency in Guillain-Barré syndrome. Ann Neurol. 2010. 67(6):781-7
  17. van den Berg B, Walgaard C, Drebthen J, et al Guillain-Barré syndrome: pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol. 2014 Aug;10(8):469-82
  18. Hughes RA, Pritchard J, Hadden RD. Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev 2013. :CD008630
  19. Patwa HS, Chaudhry V, Katzberg H, et al. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012. 78(13):1009-15

Contributor(s)

  1. Bravata, Kurt R., MD
  2. Haynes, James W., MD
  3. Okonkwo, Emem, MD
  4. Wedro, Benjamin, MD
  5. Cherian, Geo, MD

Updated/Reviewed: April 2020