Overview
Guillain-Barre Syndrome (GBS) is a heterogenous group of conditions characterised by immune-mediated destruction of peripheral nerves (cranial nerves can be involved as well). Acute paralysis and diminished tendon reflexes are a hallmark for the condition. Commonly, symptoms arise after a bout of illness (usually respiratory or gastrointestinal infections).
In terms of epidemiology, GBS is found all over the world with no racial preponderance and has been reported in all age groups (Infants are at the lowest risk of developing GBS). It is estimated 100,000 new cases are reported worldwide each year. Despite its rare occurrence it is important to have an understanding of the disease as it is fatal if not managed in due time.
Etiology
GBS is a post-infectious immune mediated disease targeting the peripheral nerves. Up to 70% of patients report of a preceding illness weeks prior to onset of symptoms.
Common pathogens associated with GBS
- Campylobacter jejuni – this is the most common bacterial cause. Presents as gastrointestinal or respiratory infection and is associated with the following antibodies targeting gangliosides on myelin: GM1, GD1a, GalNac-GD1a, and GD1b.
- Cytomegalovirus – most common viral cause. Usually presents as a respiratory infection and is associated with antibody GM2
- Covid-19
- Epstein-Barr virus
- Varicella zoster virus
- HIV
- Zika virus
- Mycoplasma pneumoniae
Other causes linked to the development of GBS include:
- Vaccines – the flu vaccination administered in 1976 against Influenza led to a a surge of GBS cases
- Medications – penicillin, anti-motility drugs, fluoroquinolones, oral contraceptives
- Surgery
- Trauma
- Pregnancy
Pathophysiology
Up to 70% of cases report of a prior infection hence we see molecular mimicry plays a role in the development of GBS. The infectious agents mentioned above generate antibodies which cross-react with gangliosides and glycoproteins found on the myelin sheath of peripheral nerves. In a C.jejuni infection in particular, antibodies generated against capsular lipooligosaccharide antigens cross-react with gangliosides on myelin sheath leading to macrophage-mediated multifocal stripping of the myelin sheath.
This leads to defective propagation of electrical impulses (delays or complete absence) resulting in flaccid paralysis of the muscles being supplied by the demyelinated nerves. In some severe cases, axonal disruption and loss may occur.
Pathologically we see lymphocytic infiltration of spinal roots and peripheral nerves (cranial nerves may be involved as well), followed by macrophage-mediated, multifocal stripping of the myelin sheath.
Subtypes of GBS
Acute inflammatory demyelinating polyneuropathy (AIDP)
- Most common subtype.
- Generally preceded by an infection.
- Characterised by progressive, symmetrical, ascending paralysis and areflexia (starts at the feet and spreads), sensory changes such as paraesthesia (usually precede motor symptoms by a day or so), autonomic dysfunction (such as sinus tachycardia, postural hypotension, excessive sweating, urinary retention and constipation) as well as pain especially in the lower back and hip joint.
- Demyelination occurs at the level of the nerve root, and sensory nerves are preserved.
- About 20% of patients develop respiratory failure
Acute motor axonal neuropathy (AMAN)
- Second most common subtype.
- Common in children
- Purely motor with no sensory symptoms
- Associated with preceding infection
- Characterised by rapidly progressive, symmetrical weakness, areflexia (though rarely reflexes are preserved). Respiratory failure may develop if not managed timely.
- The following antibodies are seen in AMAN: GD1a, GD1b, GM1.
- It is distinguished from AIDP by axonal involvement on nerve conduction study.
Acute motor sensory axonal neuropathy
- Affects sensory and motor nerves
- A preceding infection is usually reported
- Severe motor and sensory dysfunction occurs
- Involves axonal degeneration of both sensory and motor fibers with little demyelination
Miller-Fisher syndrome
- Presents as triad of ataxia, areflexia and ophthalmoplegia
- Additional features include: diplopia, dysarthria, dizziness, facial paresis, distal hyporeflxia
- Associated with GQ1b antibodies which attack the GQ1b ganglioside found in the oculomotor, trochlear and abducens nerve
- Advanced cases present with autonomic symptoms, as well as those mentioned above, such as postural hypotension, cardiac arrthymias
Acute panautonomic neuropathy
- Involves the autonomic system
- Characterised by postural hypotension, bowel + bladder retention, anhidrosis, reduced salivation and lacrimation, dysrhythmias
- Does not involve the motor or sensory nerves usually
Pure sensory GBS
- Involves the sensory nerves only
- Characterised by rapid and symmetrical sensory loss, sensory ataxia and areflexia with no motor involvement
Pharyngeal-cervical-brachial variant
- Predominantly affects the upper limb, cervical, facial and oropharyngeal regions with no or mild lower limb involvement.
- Characterised by symmetrical muscle weakness from the oropharyngeal and neck area to the proximal upper extremities with upper limb areflexia and bulbar symptoms such as dysphagia and dysarthria.
- May be associated with anti-GT1A antibodies
Clinical presentation
History
Up to two thirds of patients with GBS report an antecedent illness or event 1-3 weeks prior to the onset of weakness.
- Ascending and symmetrical muscle weakness
- Inability to stand or walk
- Shortness of breath due to respiratory muscle involvement
- Cranial nerve involvement
- Ophthalmoplegia
- Facial droop
- Dysarthria
- Dysphagia
- Diplopia
- Sensory symptoms such as
- Paresthesias
- Numbness
- Loss of vibration sense
- Loss of proprioception
- Pain – described as aching/throbbing
- Autonomic changes
- Tachycardia
- Bradycardia
- Facial flushing
- Paroxysmal hypertension
- Orthostatic hypotension
- Anhidrosis and/or diaphoresis
- Urinary retention
- Constipation
Physical examination
- Respiratory exam
- Diminished breath sounds
- Reduced chest wall expansion
- Gastrointestinal exam
- Absent bowel sounds (paralytic ileus)
- Suprapubic fullness/tenderness – retained urine
- Neurological exam
- Cranial nerve III, VI palsy causes limited eye movements
- Cranial nerves XII, V, IX, and X palsies cause dysphagia, dysarthria, facial droop.
- Marked symmetrical muscle weakness with hypotonia
- Absent and/or reduced reflexes
Diagnosis
GBS is primarily a clinical diagnosis but a number of investigations can be carried out to confirm:
- Nerve conduction studies and electromyography
- Lumbar puncture – spinal fluid shows a normal amount of white blood cells and an elevated CSF protein level.
- Serological studies – to detect autoantibodies
- Peripheral neuropathy work -up:
- Thyroid panel
- Rheumatology profiles
- Vitamin B-12
- Folic acid
- Hemoglobin A1C
- Erythrocyte sedimentation rate (ESR)
- Immunoelectrophoresis of serum protein
- Tests for heavy metals
- Imaging studies such as MRI – enhancement of the nerve roots indicating inflammation and a break in the blood-nerve barrier due to GBS.
Treatment
Medical therapy
Immunotherapy with:
- Plasma exchange (plasmapharesis) which will remove all the autoantibodies, immune complexes and any other inciting factor.
- IVIG (IV immunoglobulin)
IVIG is preferred in hemodynamically unstable patients.
IVIG should not be given before plasma exchange as it will remove the IVIG.
In resource poor settings one can use partial exchange blood transfusion.
Supportive therapy
- Physical therapy
- Occupational therapy
- Speech therapy
- Prevention of thromboembolism using compression stockings and low molecular weight heparin.
- Ventilatory support
- Cardiac monitoring
- Adequate nutrition parenterally or enterally.
Complications
- Respiratory compromise
- Bulbar palsies
- Significant disability that persists despite receiving standard treatment
Prognosis
80% of patients can independently walk after 6 months with about 60% fully recovering in a year. The presentation can range from mild cases where there is only mild to moderate difficulty while walking to life-threatening muscle paralysis.
Mortality in the acute phase of the disease is at 5% while those who survive, despite full recovery could suffer from paraesthesias, fatigue and pain for years to come.
- Poor prognostic factors
- Older age ( 50 years and above)
- Preceding infection
- Poor upper limb strength
- Require mechanical ventilation
- Hospital stay of longer than 11 days
Relapse can occur but is very rare. It is seen in patients who had delayed treatment, co-morbidties that worsen the condition and a lengthened acute period.
Differential diagnoses
- Acute myelopathy from compression or ischemic injury
- Chronic inflammatory demyelinating polyradiculopathy
- Vitamin B12 and folate deficiency causing decreased myelination of nerves
- Poliomyelitis
- HIV associated neuropathy
- Spinal cord compression
- Bilateral strokes
- Heavy metal toxicity
- Lyme disease
- Multiple sclerosis
- Botulism
- West Nile virus
- Acute intermittent porphyria
