Guillain-Barré Syndrome

Basics

Description

  • A group of acquired autoimmune disorders causing acute peripheral neuropathy and ascending paralysis that progressively worsens for up to 4 weeks followed by a slow spontaneous recovery of function
  • Subtypes classified by pattern of neural injury:
    • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP): progressive limb weakness with areflexia (~95% of GBS cases in Europe and North America)
    • Axonal subtypes:
      • Acute motor axonal neuropathy (AMAN): pure motor neuropathy strongly associated with Campylobacter jejuni and a higher rate of respiratory failure (~5% of cases in Europe and North America but 30–47% of cases in China, Japan, and Central and South America)
      • Acute motor-sensory axonal neuropathy (AMSAN): combined motor–sensory neuropathy; poor prognosis with prolonged course
    • Regional subtypes:
      • Miller Fisher syndrome (MFS): triad with ophthalmoplegia, ataxia, and areflexia; antibodies to GQ1b present in 90% of patients with MFS
      • Bickerstaff encephalitis: possible variant of MFS with encephalopathy, ophthalmoplegia, ataxia, and hyperreflexia
      • Pharyngeal-cervical-brachial GBS: Parasympathetic and cholinergic dysfunction leads to neck, arm, and oropharyngeal weakness along with upper extremity areflexia.
    • Sensory subtypes:
      • Acute pandysautonomia: orthostatic hypotension, gastroparesis, ileus, constipation/diarrhea, sudomotor/pupillary abnormalities, and neuropathic pain
      • Acute sensory ataxic neuropathy (ASAN): controversial variant with sensory loss and ataxia
  • Polyneuritis cranialis: bilateral cranial nerve involvement and severe peripheral sensory loss associated with cytomegalovirus (CMV) infections
  • Synonym(s): GBS, AIDP; Landry-Guillain-Barré-Strohl syndrome, acute inflammatory idiopathic polyneuritis; acute autoimmune neuropathy; Landry ascending paralysis

ALERT
Rapidly progressing paralysis and respiratory failure occur in 20–30% of patients. Some require mechanical ventilation within 48 hours.

Alert
Areflexia is a red flag for GBS in patients with rapidly progressive limb weakness.

Alert
A history of weakness preceded by respiratory or GI infection suggests GBS.

Epidemiology

Incidence
  • Most common acute paralytic disease in Western countries
  • 0.6 to 2.0/100,000 worldwide
  • U.S. incidence: 0.9 to 1.8/100,000
  • Increases with age: 0.8/100,000 in children <18 years of age; 3/100,000 in adults >60 years
  • 1.5 times higher incidence in males

Etiology and Pathophysiology

  • Post-infectious autoimmune process targets Schwann cell surface membrane, myelin, and/or gangliosides causing peripheral nerve destruction and demyelination.
  • Pathogenesis thought to involve molecular mimicry (i.e., an immune response to antigenic targets that are coincidentally shared by infectious organisms and host peripheral nerve tissue). Antibodies cross-react with GM1 myelin ganglioside with resultant damage to peripheral nervous system.

Genetics
Host factors appear to play a role in GBS, but no clear genetic risk has been identified.

Risk Factors

Influenza vaccinations

  • Inactivated seasonal flu vaccines associated with an increase in GBS risk equivalent to one case/million vaccines above background incidence (far less than the 17 cases of GBS per million people infected with influenza virus)
  • Incidence of GBS associated with flu vaccine decreasing over time with no increase detected in 2017–18 season
  • Of historical note: Increased incidence during 1976 U.S. National H1N1 Immunization Program had vaccine-attributable risk of 8.8 per million recipients compared to 1.6 per million recipients in the 2009 H1N1 vaccination campaign.

Commonly Associated Conditions

Infection of the respiratory (22–53%) or GI (6–26%) tract in preceding 6 weeks

  • Campylobacter jejuni: most common precipitant of GBS (21–40% of cases):
    • Associated with axonal degeneration, slower recovery, more severe residual disability
  • Cytomegalovirus (CMV): Primary CMV infection precedes 10–22% of cases.
  • Rarely associated with Mycoplasma pneumoniae, influenza infection, Epstein-Barr virus, varicella-zoster virus, HIV infection, Zika virus, and some arboviral infections

Diagnosis

History

  • AIDP presents with onset of progressive limb weakness that reaches its worst within 4 weeks (73% reach a functional nadir in 1 week; 98% by 1 month).
  • Preceding respiratory or gastrointestinal infection
  • Earliest symptoms include pain, numbness, paresthesias, or proximal muscle weakness that can spread to involve cranial nerves and muscles of respiration.
  • Cranial nerve symptoms: facial nerve palsy; diplopia; dysarthria; dysphagia; ophthalmoplegia
  • Neuropathic pain, sometimes severe, occurs in 30–50%, most commonly in the back and lower extremities.
  • Purely sensory symptoms exclude GBS.

Physical Exam

Diagnostic criteria for typical GBS:

  • Required for diagnosis:
    • Progressive weakness reaching nadir between 12 hours and 28 days
    • Affects >1 limb
    • Areflexia/hyporeflexia
  • Strongly supportive:
    • Paresthesias with only mild changes in objective sensory function (e.g., pinprick, light touch)
    • Relative symmetry
    • Cranial nerve involvement, especially bilateral/symmetric weakness of facial muscles
    • Recovery beginning within 4 weeks after progression ceases
    • Autonomic dysfunction (tachycardia, bradycardia, facial flushing, hypertension, hypotension, anhidrosis, diaphroesis), urinary retention, diarrhea, constipation
    • Absence of fever at onset

Differential Diagnosis

Differential diagnosis of acute flaccid paralysis:

  • Brain: basilar artery stroke, brainstem encephalitis
  • Spinal cord: transverse myelitis, spinal cord compression
  • Motor neuron: poliomyelitis, acute flaccid myelitis
  • Peripheral neuropathy other than GBS: vasculitis, critical illness polyneuropathy, infectious disease (e.g., diphtheria, Lyme disease, HIV), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), acute intermittent porphyria
  • Neuromuscular junction: myasthenia gravis, Eaton-Lambert syndrome, botulism, toxins (e.g., heavy metals, inhalant abuse, organophosphates)
  • Muscle: electrolyte disturbance (hypokalemia, hypophosphatemia), inflammatory myopathy, critical illness myopathy, acute rhabdomyolysis, trichonosis, periodic paralysis
  • Psychological causes of weakness

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)
  • Studies to establish the diagnosis:
    • Lumbar puncture (LP): Increased CSF protein (most patients with GBS will have CSF protein >400mg/L) without pleocytosis is present in ~80% of cases (Note: CSF protein is often normal within the first 48 hours of symptom onset).
    • Nerve conduction study (NCS): Most useful confirmatory test; conduction velocities abnormal in 85% of patients with demyelination, even early in the disease. If nondiagnostic, repeat after 1 to 2 weeks.
  • Imaging generally not required. MRI demonstrates spinal nerve root and/or cauda equina enhancement.
  • Studies to find underlying cause:
    • Stool culture and serology for C. jejuni
    • Acute and convalescent serology for CMV, EBV, HIV, and M. pneumoniae
    • Anti-GQ1b antibodies in MFS variant and anti-GM1 antibodies in AMAN
    • Peripheral neuropathy: TFT; rheumatoid factor, B12/folate; Hemoglobin A1C; ESR; RPR; heavy metal assay

Follow-Up Tests & Special Considerations
  • Analyze CSF prior to treatment with intravenous immunoglobulin (IVIG), which can cause aseptic meningitis.
  • A repeat NCS 3 to 8 weeks after onset can classify the subtype of GBS.

Diagnostic Procedures/Other
Sural nerve biopsy not indicated except to rule out vasculitis or amyloidosis.

Treatment

General Measures

  • Consider admission to ensure that disease does not progress (respiratory function, autonomic stability, paralysis).
  • Supportive care is essential, paying close attention to complications of immobility, neurogenic bladder/bowel and pain management.
  • Pain treatment: NSAIDs helpful but often insufficient. Gabapentin and carbamazepine decrease opioid requirements in patients with GBS. One is not superior to others (1)[A].
  • DVT prophylaxis recommended in nonambulatory patients (2)[C].
  • Neostigmine or erythromycin may be effective for ileus, if present (2)[C].

Medication

First Line
  • IVIG 0.4 g/kg/day for 5 days or (less commonly) 1g/kg/day for 2 days:
    • In severe disease, IVIG started within 2 weeks of onset hastens recovery as much as plasma exchange (PE) (3)[A].
    • In children, IVIG hastens recovery compared with supportive care alone (3)[A].
    • Combined treatment with IVIG and PE confers no clinically significant benefit (3)[A].
  • PE:
    • Compared with supportive treatment alone, those treated with PE are quicker to recover walking (NNT 7), have less requirement and shorter duration for mechanical ventilation (NNT 8), recover full muscle strength more quickly (NNT 8), and have fewer severe sequelae at 1 year (NNT 17) (4)[A].
    • Higher risks of relapse found with PE versus supportive care with no difference in severe infection or mortality (4)[A].
    • In mild GBS, two sessions of PE are superior to none. In moderate GBS, four sessions are superior to two. In severe GBS, six sessions are not significantly better than four (4)[A].
    • PE is most beneficial if started within 7 days of disease onset. PE still helpful up to 30 days (4)[A].
    • Value of PE in children <12 is unknown.

Second Line
  • Corticosteroids: not beneficial as monotherapy or as combined treatment. Low-quality evidence suggests steroids delay recovery (5)[A].
  • CSF filtration is no different than PE (6)[B].
  • Interferon β and brain-derived neurotrophic factor no different than placebo (6)[B].

Additional Therapies

  • Physical and occupational therapy improves fatigue and functional abilities (2)[C].
  • Speech and language therapy improves swallowing function, if affected (2)[C].

Complementary and Alternative Medicine

Tripterygium polyglycoside hastened recovery significantly more than corticosteroids (NNT 4) in one small trial (6)[A].

Admission, Inpatient, and Nursing Considerations

  • Admit patients with suspected GBS.
  • Closely monitor respiratory status with serial measurement of vital capacity (VC) and static inspiratory and expiratory pressures (PImax and PEmax).
  • Predictors of respiratory failure:
    • Rapid progression: ≥3 days between onset of weakness and hospital admission
    • Facial and/or bulbar weakness
    • VC decrease >30%
    • Medical Research Council (MRC) sum score indicating muscle weakness: 0 to 5/5 muscle strength grading for bilateral upper arm abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and foot dorsal flexors totaling 60 points
  • Indications for intubation:
    • VC <20 mL/kg
    • PImax <30 cm H2O
    • PEmax <40 cm H2O
  • Prevent complications of immobilization with DVT prophylaxis and frequent turning.
  • Respiratory care, aspiration precautions, pulmonary toilet
  • Monitor bowel and bladder function for ileus and urinary retention.
  • Begin immediate physical therapy to preserve passive range of motion.
  • Mildly affected patients who can walk unaided and are stable for >2 weeks are unlikely to experience disease progression and may be managed as outpatients. Monitor bowel and bladder function for ileus and urinary retention.

Ongoing Care

Follow-up Recommendations

Patient Monitoring
  • Patients require close monitoring of respiratory, cardiac, and hemodynamic function, typically in the ICU setting.
  • Pulmonary function testing (VC, respiratory frequency) q2–6h in the progressive phase and q6–12h in the plateau phase
  • Monitor bulbar weakness and ability to handle airway secretions.
  • Telemetry in patients with severe disease

Patient Education

Emphasize expectation for significant recovery and explain phases of illness.

Prognosis

  • If untreated, three phases of illness:
    • Initial progressive phase up to 4 weeks with highest risk of death and complication
    • Variable plateau phase
    • Recovery phase (weeks to months): return of proximal then distal strength
  • Most recovery occurs within the first year.
  • 80% recover within 6 to 12 months with maximum 18 months past onset.
  • 20–39% with residual disability after 1 year:
    • Bilateral footdrop, intrinsic hand muscle wasting, sensory ataxia, dysesthesia, fatigue, musculoskeletal pain
    • Half of these with severe disability
  • Factors associated with poor functional outcome:
    • Age >60 years, rapid progression, severe disease, severe disability on either admission or discharge, preceding diarrhea, male sex, positive C. jejuni or CMV serology, axonal degeneration, need for mechanical ventilation

Complications

  • 3–7% mortality in Europe and North America. Older patients, those with severe disease have highest risk.
  • 20–30% require mechanical ventilation.
  • 70% develop autonomic dysfunction with hemodynamic instability, urinary retention, ileus, and anhidrosis.
  • 10% have relapse.
  • ~2% develop relapsing CIDP.

Additional Reading

  • Sejvar JJ, Baughman AL, Wise M, et al. Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123–133. [PMID:21422765]
  • Vellozzi C, Iqbal S, Broder K. Guillain-Barré syndrome, influenza, and influenza vaccination: the epidemiologic evidence. Clin Infect Dis. 2014;58(8):1149–1155. [PMID:24415636]
  • Willison HJ, Jacobs BC, van Doom PA. Guillain-Barré syndrome. Lancet. 2016;388(10045):717–727. [PMID:26948435]

Codes

ICD-10

  • G61.0 Guillain-Barré syndrome

ICD-9

  • 357.0 Acute infective polyneuritis

SNOMED

  • 40956001 Guillain-Barre syndrome (disorder)

Clinical Pearls

  • Suspect GBS in cases of ascending flaccid paralysis with areflexia and an antecedent history of viral respiratory illness or gastroenteritis.
  • When GBS is suspected, evaluate VC and inspiratory force for signs of respiratory compromise.
  • Uncomplicated GBS has a slow spontaneous recovery. Treatment with IVIG or PE speeds rate of recovery and reduces disability.
  • The most useful diagnostic tests for GBS are nerve conduction studies and lumbar puncture.
  • GBS risk following native influenza virus infection is 40 to 70 times greater than after seasonal influenza vaccination.

Authors


Grant M. Reed, DO
Simon B. Griesbach, MD

Bibliography

  1. Liu J, Wang LN, McNicol ED. Pharmacological treatment for pain in Guillain-Barré syndrome. Cochrane Database Syst Rev. 2015;(4):CD009950. [PMID:25855461]
  2. Hughes RA, Wijdicks EF, Benson E, et al; for Multidisciplinary Consensus Group. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol. 2005;62(8):1194–1198.  [PMID:16087757]
  3. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2014;(9):CD002063. [PMID:25238327]
  4. Chevret S, Hughes RA, Annane D, et al. Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2017;(2):CD001798. [PMID:28241090]
  5. Hughes RA, Brassington R, Gunn A, et al. Corticosteroids for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2016;(10):CD001446. [PMID:27775812]
  6. Pritchard J, Hughes RA, Hadden RD, et al. Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2016;(11):CD008630. [PMID:28501031]


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