Guillain-Barré syndrome

  • The most common cause of acute flaccid paralysis worldwide
  • Acute inflammatory demyelinating polyneuropathy (AIDP) is the prototype form of GBS, a predominantly motor disorder with arreflexia
  • Incidence in North America and Europe is 0.8-0.9 cases per 100,000 population
  • More common in indivituals above 50 years of age
  • Incidence increases by 20% for every 10 years increase in age
  • Male:female ratio is 1.78:1
  • Mortality from complications is 3-8%
  • Weakness reaches nadir in 10-15 days in 98% of cases
  • A plateau phase is reached by 3-4 weeks which may last several days
  • Recovery usually begins 2-4 weeks after progression ceases
  • Progression beyond 4 weeks may signal progression to chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Recovery is variable from complete and rapid to incomplete and slow. Little or no further recovery can be expected after 2 years.
  • The mean time to clinical recovery is 200 days
  • Most patients recover almost completely
  • 5-10% of patients suffer permanent weakness, imbalance or sensory loss
  • 50% of patients have mild residual signs of neuropathy
  • 3% of patients have one or more relapses which are clinically identical with the monophasic form of the disease
  • 3-6% of patients with GBS develop chronic inflammatory demyelinating polyneuropathy (CIDP)

GBS types

  • Acute inflammatory demyelinating polyneuropathy (AIDP)
  • Acute motor-sensory axonal neuropathy (AMSAN)
  • Acute motor axonal neuropathy (AMAN)

GBS variants

Many variants have been described, the following list is nonexhaustive.

  • Miller Fisher syndrome
  • Acute ataxic neuropathy
  • Acute autonomic neuropathy
  • Facial diplegia with paresthesias
  • Multiple cranial neuropathy
  • Paraparetic variant
  • Pharyngeal-cervical-brachial variant

Etiology

The exact etiology of GBS remains uncertain.

  • The association with vaccination is debated. Some reports of definite GBS in association with influenza, hepatitis B and Gardasil vaccines have been published
  • An infectious disease, most commonly upper respiratory tract viral illness or diarrhea, precedes GBS by 1-4 weeks in up to 2/3 of patients
  • The most frequently identified bacterial infection is by Campylobacter jejuni, implicated in ~30% of GBS cases. Serologic evidence of C. jejuni infection may exist without history of enteritis
  • The most frequently identified viral infection is by CMV. Serologic evidence is found in ~10% of GBS cases
  • CMV is more frequently found in younger patients and is associated with more severe disease
  • Mycoplasma pneumoniae respiratory infection may precede GBS in up to ~5% of cases

Infections and systemic illnesses associated with GBS

Bacterial infections

  • Campylobacter jejuni
  • Mycoplasma pneumoniae
  • Salmonella typhi (possibly)
  • Shigella (possibly)
  • Brucella (possibly)
  • Yersinia enterocolitica (possibly)
  • Legionella
  • Lyme (possibly)

Viral infections

  • Cytomegalovirus
  • Influenza
  • Parainfluenza
  • Epstein-Barr
  • Cocksackie
  • Echo
  • Measles
  • Mumps
  • Rubella
  • Herpes simplex
  • Varicella zoster
  • Hepatitis A and B
  • Human immunodeficiency virus
  • Zika (possibly)

Parasitic infections

  • Cyclospora

Systemic diseases

  • Surgery
  • Trauma
  • Vaccination
  • Pregnancy
  • Thyroid disease (possibly)
  • Hodgkin’s lymphoma (possibly)
  • Leukemia
  • Lung cancer (possibly other solid tumors)
  • Sarcoidosis (possibly)
  • Systemic lupus erythematosus (possibly)
  • Paraproteinemia (possibly)

Presentation

  • Progressive symmetrical muscle weakness
  • Proximal weakness is more frequent and usually more severe than distal weakness
  • Arreflexia is a hallmark sign of GBS
  • Reflexes are virtually always unobtainable in limbs that are too weak to resist gravity
  • Ascending paralysis is more common. Descending paralysis occurs in 10-15% of cases
  • Tingling, prickling or pins and needles sensations in extremities are frequently reported initial symptoms
  • 1/3 of patients report pain with neuropathic characteristics that may precede the weakness by up to 3 weeks
  • Often the initial weakness pattern is asymmetric and becomes more symmetric as disease progresses
  • 50% of patients will have cranial nerve involvement at some point in the disease. The facial nerve is most commonly affected
  • 15-30% of patients with GBS will need ventilatory support
  • 65% of patients with fully developed GBS have signs of dysautonomia (most frequently patients with more severe disease):
    • Sinus tachycardia or bradycardia
    • Sinus arrest
    • Supraventricular tachycardia
    • Life threatening 3rd degree AV block or ventricular tachycardia
    • “Vagal spells” (bronchorrhea, bradycardia, hypotension)
    • Paroxysmal hypertension or hypotension
    • Orthostatic hypotension
    • Ileus
    • Urinary retention
  • Unusual features of GBS include:
    • Hearing loss
    • Vocal cord paralysis
    • Meningeal signs
    • Papilledema
    • Mental status changes
    • Posterior reversible encephalopathy (PRES)

Electrophysiologic findings

  • Nerve conduction studies may be completely normal or nonspecifc early in the disease
  • Repeat studies are often necessary
  • 95-100% of patients have bilaterally absent H-reflexes during the first 1-2 weeks of disease
  • 40-80% of patients have prolongued F-waves early in the disease and it may be the only abnormal finding in up to 1/4 of patients
  • Multiple or complex A-waves are found in approximately 2/3 of GBS patients but are not specific to GBS
  • Motor conduction blocks are highly specific but found in only about 1/3 of patients with GBS
  • Conduction velocity slowing is found in up to 25% of patients and is particularly uncommon during the first 2 weeks in GBS. Conduction may paradoxically be slower between weeks 3-6 during recovery
  • Prolonged distal motor latency is a common but nonspecific finding
  • CMAP duration may be prolonged
  • 75% of patients have abnormal SNAPs at some time during their illness
  • Needle EMG is the least helpful study in the evaluation of GBS

Cerebrospinal fluid findings

  • Cell count is usually normal but pleocytosis does not exclude the diagnosis
  • <10% of patients may have slight lymphocytic pleocytosis greater than 10 cells/mm
  • Patients with GBS following certain infections (eg HIV, Lyme) or systemic lymphoma, may have more prominent pleocytosis
  • 50% of patients have elevated protein during the first week in the disease
  • 75% of patients have elevated protein by the 3rd week in the disease
  • CSF protein peaks during the 2nd and 3rd weeks. Normalization may take several months
  • Patients with extremely high protein levels (≥1500mg/dl) may develop papilledema and symptoms of pseudotumor cerebri

Other laboratory findings

  • Routine studies are often normal
  • Hepatic transaminases and ESR are sometimes elevated, possibly reflecting a preceding infectious disease
  • CPK may be slightly elevated, especially in patients with muscle pain and tenderness
  • EBV and CMV antibody titers may be increased
  • HIV titer should be obtained especially in the setting of CSF pleocytosis
  • Achetylcholine receptor antibody titers and titers for C. botulinum may be helpful in patients with ocular-pharyngeal-brachial variant

Antiganglioside antibodies in serum

Antibodies against many different gangliosides have been discovered in sera of GBS patients. Some of them are found in specific subgroups of GBS.

  • Antibodies to GD3, GT1a and GQ1b are associated with GBS with ophthalmoplegia
  • Antibodies to GQ1b are found in 95% of patients with Miller Fisher syndrome
  • Antibodies to GM1, GM1b, GD1a or GalNAc-GD1a are found in 50% of patients with AMAN
  • IgG antibodies to GM1 or GD1a are associated with AMAN, AMSAN and acute motor-conduction-block neuropathy but not AIDP

Imaging

  • MRI is useful in excluding CNS disorders that may mimic GBS - mainly brainstem or spinal pathology
  • Nerve root enhancement of cauda equina and occasionally of the facial nerve may be detectable

Differential

Peripheral neuropathy

  • Drug induced polyneuropathy (see Drug considerations in NMD section)
  • Organophosphate poisoning
  • Hexacarbons (“glue sniffer’s” neuropathy)
  • Heavy metal poisoning (arsenic, lead, gold, thalium)
  • Diphtheritis
  • Lyme disease
  • Tick paralysis
  • Acute intermittent porphyria
  • Critical illness polyneuropathy
  • Vasculitic neuropathy

Polyradiculopathies and ganglionopathies

  • Acute sensory neronopathy syndrome
  • Carcinomatous or lymphomatous meningitis

Disorders of neuromuscular transmission

  • Botulism
  • Hypermagnesemia
  • Myasthenia gravis
  • Antibiotic induced paralysis
  • Snake venom

Myopathies

  • Polymyositis
  • Drug induced myopathy
  • Critical illness myopathy

Metabolic abnormalities

  • Hypokalemia
  • Hypophosphatemia
  • Hypermagnesemia
  • Hypomagnesemia

CNS disorders

  • Basilar artery thrombosis and locked-in syndrome
  • Brainstem encephalomyelitis
  • Transverse myelitis
  • Acute necrotic myelopathy
  • Cervical cord or foramen magnum compression

Other

  • Malingering
  • Conversion disorder

Management

General supportive measures

  • Monitor FVC and/or NIF and MEP. Watch out for early signs of impending respiratory insufficiency (seeRespiratory management in NMD section) and if appropriate, intubate and ventilate
  • Prevent atelectasis
  • Help mobilize secretions with assisted coughing
  • Monitor cardiac function and blood pressure. Watch out for serious cardiac arrhythmia and other signs of dysautonomia
  • Prefer antihypertensives with short half-lives (labetalol, esmolol, nitroprusside infusion) to treat severe hypertension
  • Hypotension can be managed by maintaining intravascular volume
  • Profound hypotension should warrant search for other causes (eg sepsis, LE, MI)
  • Prevent GI bleeding with prophylactic proton pump inhibitors, antacids or sucralfate
  • Prevent thromboembolic complications with prophylactic heparin or LMWH
  • Prevent constipation/ileus
  • Watch out for urinary retention
  • Prevent decubitus with specialized mattress and frequent position changes
  • Watch out for infections. Consider weekly chest X-ray and urinalysis
  • Prophylactic antibiotics are not needed
  • Tube feeding if swallowing is impaired
  • Monitor BUN, creatinine, serum albumin, electrolytes
  • Provide adequate analgesia! Pain in GBM is a common complication, may be severe and is underappreciated

Specific treatment

Plasma exchange (PE) and IVIg are equally effective in reducing the degree of disability at 4 weeks and the need for and duration of assisted ventilation, mortality, and residual disability.

  • PE must be initiated within 2-4 weeks from symptom onset and is most effective when started within the first 2 weeks
  • The optimal volume of plasma and number of PE have not been established
  • Many physicians use the protocol of North American trial in which a total of 200–250 mL/kg was exchanged over 7–10 days
  • Some evidence suggests that the number of PE should be adjusted to disease severity
  • Continuous flow PE is superior to intermittent flow exchange
  • Albumin may be superior to fresh frozen plasma as the exchange fluid
  • IVIg 0.4 g/kg body weight daily for 5 consecutive days, has replaced PE as the preferred treatment in many centers, mainly because of its greater convenience and availability
  • Corticosteroid therapy is ineffective for treating GBS



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