Guillain-Barre Syndrome (GBS)

Guillain-Barre Syndrome (GBS)

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•      Epidemiology: 1-2 per 100,000 per year; M>F
•      A heterogenous disease, with different variants; 
•         i.e. Miller Fisher syndrome — The typical presentation of MFS is that of ophthalmoplegia with ataxia and areflexia

Clinical Features: progressive, fairly symmetric muscle weakness accompanied by absent or decreased deep tendon reflexes (DTRs). Patients usually present a few days to a week after the onset of their symptoms. The weakness is variable (i.e. mild difficultly with walking to nearly complete paralysis of all extremity, facial, respiratory, bulbar muscles, etc).

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•      The weakness usually starts in the legs (NOTE: in 10% of patients, weakness starts in the arms or face)
•      Severe respiratory muscle weakness necessitating ventilator support occurs in 10-30%
•      Paresthesias in the hands and feet accompany weakness in >80% of cases
•      Pain (often in the back and extremities) can be presenting feature in the acute phase
•      Dysautonomia: tachycardia, urinary retention, HTN alternating with hypotension, orthostatic hypotension,  bradycardia, other arrhythmias, ileus, loss of sweating, etc. This can be associated with sudden death
•      Unusual Associations: SIADH, hearing loss, vocal cord paralysis, etc 

Course: progresses, usually over 2 weeks. At 4 weeks after the initial symptoms, 90% of patients have reached the nadir of their disease

Pathogenesis: thought to result from an immune response to a preceding infection that cross-reacts with peripheral nerve components because of molecular mimicry (immune response can be directed toward myelin or the axon of the peripheral nerveà resulting in demyelinating and axonal forms)

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       Most commonly identified precipitant: Campylobacter jejuni

o   Other: CMV, EBV, HIV

o   Triggers: after a immunization, surgery, trauma, bone marrow transplant

Investigations: diagnosis is confirmed with CSF and NCS/EMG; always do an LP!

1.LPàCSF: elevated protein with a normal WBC count (albuminocytological dissociation)—in up to 66% of cases, at 1 week after symptom onset

·       Elevated protein: may be due to increased permeability of the blood brain barrier (BBB) at the level of the proximal nerve roots

NOTE: a CSF pleocytosis is common in patients with GBS and HIV

2.EMG & NCS: help confirm diagnosis and provide prognostic info

Diagnostic criteria for GBS from the National Institute of Neurological Disorders and Stroke (NINDS) – based on expert consensus

• Progressive weakness of >1 limb, ranging from minimal weakness of the legs to total paralysis of all four limbs, the trunk, bulbar and facial muscles, and external ophthalmoplegia 
•  Areflexia (universal areflexia is typical): distal areflexia with hyporeflexia at the knees and biceps will suffice if other features are consistent.

Supportive features include:

•   Progression of symptoms over days to four weeks

•   Relative symmetry

•   Mild sensory symptoms or signs

•   Cranial nerve involvement, especially bilateral facial nerve weakness

•   Recovery starting two to four weeks after progression halts

•   Autonomic dysfunction

•   No fever at the onset

•   Elevated protein in CSF with a cell count <10/mm³

•   Electrodiagnostic abnormalities consistent with GBS

MANAGEMENT

*SUPPORTIVE CARE: up to 30% develop NM respiratory failure, requiring ventilation. Patient ought to be monitored for autonomic dysfunction (i.e. cardiac, respiratory, hemodynamic instability)
-PT/OT, wound care, DVT prophylaxis
-Adequate pain control

*RESPIRATORY FAILURE
-Vigilance is essential (deterioration can occur rapidly). Respiratory failure is common: 15-30% require ventilator support
-Measure vital capacity (VC) frequently; often measure Maximun Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP)

o   Warning, indication for intubation: FVC<20 mL/kg, MIP <30 cm H20, MEP<40 cm H20

·       -Bulbar dysfunction with swallowing problems and inability to clear secretions may add to the need for ventilator support

*AUTONOMIC DYSFUNCTION: dysautonomia occurs in 70% (i.e. tachycardia is the most common), urinary retention, hypertension/hypotension, bradycardia, orthostatic hypotension, ileus, arrhythmias, loss of sweating

*CARDIOVASCULAR MONTIORING: HR, BP, maintain intravascular volume

• Arrhythmias often occur with suctioning
• Avoid drugs that can drop BP
• Keep in mind that PLEX can cause hypotension and electrolyte abnormalities
•  Hypotension can be treated with IVF & phenylephrine (a pure alpha agonist!!)

*PAIN CONTROL: Neuropathic pain occurs in up to 50%

o   NSAIDS (don’t often work); consider gabapentin, carbamazepine

DISEASE MODIFYING TREATMENT: PLEX & IVIG

·       Plasmapharesis: removes circulating antibodies, complement & soluble biological response modifiers

o   Earlier improvement in mm strength, reduced need mechanical VE, better recovery

o   MA: most effective when started within 7 days of symptom onset

·       IVIG: precise MOA unknown; may provide anti-idiotypic antibodies, modulating expression and function of Fc RC, interfering with activation of complement & production of cytokines, interfering with activation and effector functions of T and B cells

o   As effective as PLEX

American Academy of Neurology (AAN)

o   Treatment with PLEX or IVIG hastens recovery from GBS

o   The beneficial effects of PLEX and IVIG are equivalent

o   Combining the two treatments is NOT beneficial

o   Glucocorticoid treatment alone is NOT beneficial

     Population:

o   PLEX: for non-ambulatory pts with GBS who start tx within 4 weeks of initial neuropathic symptoms;

o   For ambulatory pts who start tx within 2 weeks of onset of neuropathic sx

§  4 to 6 treatments, over 8-10 days; Side Effects- hypotension, sepsis, IV access issues

o   IVIG: non-ambulatory pts with GBS who start tx within 2 or possible 4 weeks of onset

o   0.4 mg/kg IV per day x 5 days. SE- aseptic meningitis, rash, AKI, rarely hyperviscosity

OUTCOME

• Poorer Prognosis: older age, rapid onset (<7 days), severe muscle weakness on admission, need for ventilator support, etc
• In the absence of disease modifying treatment, most patients show continued progression for up to 2 weeks, followed by a plateau phase of 2 weeks, then recovery phase (months)
• Disease Modifying treatment shortens time to walking by 50%
• Even with treatment, 5-10% have a prolonged course with very delayed and incomplete recovery

o   5% die despite intensive care

o   Relapses in 10%

IMMUNIZATIONS

o   AVOID in the acute phase of GBS and they are NOT suggested for 1 year or more after the onset of GBS

o   Future avoidance is suggested for any particular immunization that is followed within 6 weeks by the onset of GBS

RESOURCES: 
Indian Academy of Neurology. 2011 July; 14 (Suppl1): S73-S81. Treatment Guidelines for Guillain-Barre Syndrome. Meena, et al.
Treatment Guidelines for Guillain-Barre Syndrome