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Guillain-Barré Syndrome
Simon B. Griesbach, MD
Grant M. Reed, DO
image 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 opthalmoplegia, 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 CMV infections.
  • Synonym(s): GBS, acute inflammatory demyelinating polyneuropathy; Landry-Guillain-Barré-Strohl syndrome, acute inflammatory idiopathic polyneuritis; acute autoimmune neuropathy; Landry ascending paralysis
EPIDEMIOLOGY
Incidence
  • Most common acute paralytic disease in Western countries at 0.6 to 4.0/100,000 worldwide
  • U.S. incidence: 1.6 to 1.8/100,000, with 4,954 new cases reported from 2000 to 2004.
  • Increases with age: 0.8/100,000 in children <18 years of age; 3.2/100,000 in adults >60 years of age
  • 1.8 times higher incidence in males compared to females.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Autoimmune targeting of Schwann cell surface membrane, myelin, and/or gangliosides causing destruction and demyelination of peripheral nerves.
  • 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).
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 a small increase in GBS risk equivalent to 1 case/million vaccines above background incidence. This compares to 17 cases of GBS per million people infected with influenza virus.
    • Incidence of GBS associated with influenza vaccine has steadily decreased over time.
    • 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 tract (6-26%) in preceding 6 weeks
    • C. jejuni: most common precipitant of GBS, (21-32% 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, varicellazoster virus, and HIV infection
image DIAGNOSIS
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
    • Absence of fever at onset
DIFFERENTIAL DIAGNOSIS
Differential diagnosis of acute flaccid paralysis:
  • Brain: basilar artery stroke, brainstem encephalitis
  • Spinal cord: transverse myelitis, cord compression
  • Motor neuron: poliomyelitis
  • Peripheral neuropathy other than GBS: vasculitis, critical illness polyneuropathy, infectious (e.g., diphtheria, Lyme disease), CIDP, acute intermittent porphyria
  • Neuromuscular junction: myasthenia gravis, Eaton-Lambert, 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 (>0.55 g/L) without pleocytosis is present in ˜80% of cases (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
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 (1)[B].
Diagnostic Procedures/Other
Sural nerve biopsy not indicated except to rule out vasculitis or amyloidosis
image TREATMENT
GENERAL MEASURES
  • Pain treatment: NSAIDs helpful but often insufficient. Gabapentin and carbamazepine decrease opiate requirements in patients with GBS. One is not superior to the other (2)[A].
  • DVT prophylaxis recommended in nonambulatory patients (3)[C].
  • Neostigmine or erythromycin may be effective for ileus, if present (3)[C].
P.431

MEDICATION
First Line
  • IVIG 0.4 g/kg/day for 5 days
    • In severe disease, IVIG started within 2 weeks of onset hastens recovery as much as plasma exchange (PE) (4)[A].
    • In children, IVIG likely hastens recovery compared with supportive care alone (4)[A].
    • Treatment with IVIG after PE confers no clinically significant extra benefit (4)[A].
  • Plasma exchange (PE):
    • Compared with supportive treatment alone, those treated with PE have a quicker to recover walking (NNT 7), 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) (5)[A].
    • Higher risks of relapse found with PE versus supportive care with no difference in severe infection or mortality (5)[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 (5)[A].
    • PE is most beneficial if started within 7 days of disease onset. It is still helpful until up to 30 days (5)[A].
    • The value of PE in children <12 years old is unknown.
Second Line
  • Corticosteroids: not beneficial as monotherapy; do not significantly hasten recovery or affect long-term outcome. Low-quality evidence suggests they delay recovery (6)[A].
  • CSF filtration is no different than PE in one small RCT (7)[B].
  • Interferon &bgr; and brain-derived neurotrophic factor no different than placebo (7)[B]
ADDITIONAL THERAPIES
  • Physical and occupational therapy improve fatigue and functional abilities (3)[C].
  • Speech and language therapy improve swallowing function, if affected (3)[C].
COMPLEMENTARY & ALTERNATIVE MEDICINE
Tripterygium polyglycoside hastened recovery significantly more than corticosteroids (NNT 4), in one small trial (7)[A].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Admit all patients suspected of having GBS.
  • Closely monitor respiratory status with serial measurement of vital capacity (VC) and static inspiratory/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
Nursing
  • 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.
Discharge Criteria
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.
image 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
  • 80% recover within 6 to 12 months with maximum 18 months past onset
  • 20% with residual disability after 1 year:
    • Bilateral footdrop, intrinsic hand muscle wasting, sensory ataxia, dysesthesia
    • Half with severe disability
  • Factors associated with poor functional outcome:
    • Age >60 years, rapid progression, severe disease indicated by GBS disability score or MRC sum score, preceding diarrhea, positive C. jejuni or CMV serology, axonal degeneration, need for mechanical ventilation
REFERENCES
1. Shahrizaila N, Goh KJ, Abdullah S, et al. Two sets of nerve conduction studes may suffice in reaching a reliable electrodiagnosis in Guillain-Barré syndrome. Clin Neurophysiol. 2013;124(7):1456-1459.
2. Liu J, Wang LN, McNicol ED. Pharmacological treatment for pain in Guillain-Barré syndrome. Cochrane Database Syst Rev. 2015;(4):CD009950.
3. Hughes RA, Wijdicks EF, Benson E, et al. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol. 2005;62(8):1194-1198.
4. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2014;(9):CD002063.
5. Raphaël JC, Chevret S, Hughes RA, et al. Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2012;(7):CD001798.
6. Hughes RA, van Doorn PA. Corticosteroids for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2012;(8):CD001446.
7. 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;(2):CD008630.
Additional Reading
&NA;
  • Rinaldi S. Update on Guillain-Barré syndrome. J Peripher Nerv Syst. 2013;18(2):99-112.
  • 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.
  • van den Berg B, Bunschoten C, van Doorn PA, et al. Mortality in Guillain-Barré syndrome. Neurology. 2013;80(18):1650-1654.
  • Vellozzi C, Iqbal S, Broder K. Guillain-Barré syndrome, influenza, and influenza vaccination: the epidemiologic evidence. Clin Infect Dis. 2014;58(8):1149-1155.
  • Walgaard C, Lingsma HF, Ruts L, et al. Prediction of respiratory insufficiency in Guillain-Barré syndrome. Ann Neurol. 2010;67(6):781-787.
Codes
&NA;
ICD10
G61.0 Guillain-Barré syndrome
Clinical Pearls
&NA;
  • Suspect GBS in cases of ascending flaccid paralysis with areflexia and 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.
  • Most useful diagnostic tests are nerve conduction studies and LP.
  • GBS risk following influenza infection is 40 to 70 times greater than after seasonal influenza vaccination.