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EUROPEAN JOURNAL OF PHARMACEUTICAL
Tandel et al. European Journal of Pharmaceutical and Medical Research
ISSN 3294-3211
AND MEDICAL RESEARCH
EJPMR
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GUILLAIN-BARR SYNDROME (GBS): A REVIEW

Hemal Tandel*, Jigar Vanza, Nilima Pandya, Parva Jani

1
Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat, India.

*Correspondence for Author: Hemal Tandel

Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat, India.

Article Received on 19/12/2015 Article Revised on 10/01/2016 Article Accepted on 31/01/2016

ABSTRACT
Guillain-Barr syndrome (GBS) is a very rare immune mediated disorder which is associated with demyelination of
peripheral nervous system and progressive muscle weakness that occurs mostly in previously healthy individuals. It
usually presents with ascending paralysis and is severe enough to warrant hospital admission for its management.
The incidence of GBS is 1.1-1.8 cases in 100,000 per year and the incidences increases with age. GBS clinical
spectrum is heterogeneous and encompasses Acute Inflammatory Demyelinating Polyneuropathy (AIDP), Acute
Motor Axonal Neuropathy (AMAN), Acute Motor and Sensory Axonal Neuropathy (AMSAN) and Miller Fisher
Syndrome (MFS). The disease is typically characterized by a rapid onset of symmetrical limb weakness, which
progresses over days to 4 weeks, and occurs in patients of all ages. Most patients also have sensory disturbances
such as tingling or dull feelings. In developed countries GBS has become the most common cause of acute flaccid
paralysis. Despite improved recognition and treatment, GBS continues to be a severe disease. Efficacious treatments
include intravenous immunoglobulin and plasma exchange but supportive care during and following the
hospitalization is also very much crucial.

KEYWORDS: Miller Fisher Syndrome, Acute motor axonal neuropathy (AMAN), Intravenous immunoglobulin,
ganglioside antibodies.

INTRODUCTION in GBS patients and it is estimated that almost 25 - 40%

Guillain-Barr syndrome (GBS) is an acute of GBS patients world-wide have C. jejuni infection 1 - 3
demyelinating polyneuropathy (figure 1) first described weeks prior to the illness. Previously, GBS was thought
in 1859. Its features are ascending motor weakness, to be a single clinical entity. However, recent studies
sensory and autonomic dysfunction frequently followed show that GBS can be classied into atleast 4 main
by prodromal illness (usually a respiratory or clinical and electrophysiological subtypes such as acute
gastrointestinal infection). It is thought to be inammatory demyelinating polyneuropathy (AIDP),
autoimmune in-origin. GBS can cause significant acute motor axonal neuropathy (AMAN), acute motor-
morbidity requiring long hospital inpatient stay and sensory axonal neuropathy (AMSAN) and miller fisher
significant periods of rehabilitation. Approximately 10 syndrome (MSF). AIDP is characterized by
15% of patients require assistance with long term demyelination, AMAN is limited to pure motor
residual disability.[1] involvement and AMSAN is a more severe disease with
motor-sensory involvement. Seasonal variation of GBS
Many antecedent infections have been identied--, subtypes and its association with C. jejuni is little known.
including Campylobacter jejuni, cytomegalovirus Polymerase chain reaction appears to be a sensitive tool
(CMV), Mycoplasma pneumonia, Epstein-Barr virus, to detect preceding C. jejuni infection in GBS
and inuenza virus. Immunization, and parturition have patients.[11,12,21]
also been associated with GBS. GBS usually begins
abruptly with distal, relatively symmetrical onset of
paresthesias. Sensory disturbances are accompanied by
or quickly followed by progressive limb weakness.
Patients are typically able to identify a denite date of
onset of sensory and motor disturbances. Pain is
prominent in 50% of the patients. Epidemiological
studies in various countries have established an
association between Campylobacter jejuni infection and
the development of GBS. Campylobacter jejuni infection
is identied as the single most common preceding illness

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Tandel et al. European Journal of Pharmaceutical and Medical Research

there may be associated bulbar weakness and

ophthalmoplegia.[3]

Sensory symptoms may include pain, numbness and

paraesthesia. Pain commonly affects the lower back and
may be severe. Numbness and paraesthesia starts distally
and ascends in a similar fashion to the motor weakness in
80% of patients.[3,22]

Signs
On clinical examination a flaccid areflexic paralysis is
found. Muscle wasting usually occurs within two weeks
of the onset of symptoms and can be severe.

Autonomic dysfunction is common and may cause

arrhythmias, swings in blood pressure, urinary retention,
paralytic ileus and hyperhydriasis. If severe this may be
associated with sudden death.[3]

GBS subtypes[23,24]
GBS has a number of recognized subtypes that have
Figure 1: Damaged (demyelnated) nerve differing clinical and pathophysiological features:
DISEASE NAME AND SYNONYMS AIDP
Guillain-Barr syndrome (GBS) is the covering name of Acute Inflammatory Demyelinating Polyneuropathy
the syndrome. GBS is characterized by a heterogeneous (AIDP) is the most common form, accounts for around
clinical spectrum. The most frequent form in the Western 8590% of cases and is characterized pathologically by
World is the AIDP. The less frequent forms are: AMAN, demyelination, lymphocytic inltration, and
AMSAN and the cranial nerve variant Miller Fisher macrophage-mediated clearance of myelin. The clinical
Syndrome (MFS).[10] features are of symmetrical ascending motor weakness
with hypo- or areflexia. The underlying pathological
EPIDEMIOLOGY process involves inflammation and destruction of the
Ten studies reported on the incidence in children (0-15 myelin sheaths surrounding peripheral nerve axons by
years old), and found the annual incidence to be between activated macrophages. This leads to slowing and
0.34 and 1.34/100,000. Most studies investigated blockage of conduction within peripheral nerves causing
populations in Europe and North America and reported muscle weakness. Severe cases may develop secondary
similar annual incidences rates, i.e. between 0.84 and axonal damage. Nerve terminal axons which are
1.91/100,000. A decrease in incidence over the time damaged in AIDP are followed by antibody binding and
between the 1980s and 1990s was found. Up to 70% of complement xation. Activation of the complement
cases of GBS were caused by antecedent infections. The pathway mostly leads to membrane attack complex
overall incidence of GBS worldwide is 1.11.8 cases per (MAC) formation with the degradation of the terminal
100,000 per year, with higher rates in males than axonal cytoskeleton and mitochondrial injury. [3]
females. There is a bimodal age incidence, with peaks
occurring in young adults and the elderly. The incidence AMAN
rises to 3.3 cases per 100,000 per year after 50 years of Acute motor axonal neuropathy (AMAN) is more
age. There is an association with precedent infections in common in Japan and China, amongst young people and
70% of cases that are predominantly respiratory and in the summer months. It has an association with
gastrointestinal in-origin. It has been suggested there has precedent infection with Campylobacter jejuni(figure
been an association between GBS and vaccinations, 2).[13,14,20]
although the evidence for this is weak.[5]

CLINICAL FEATURES AND

PATHOPHYSIOLOGY[19]
Symptoms
The clinical features of GBS are variable. Weakness and
sensory disturbance are the most common presenting
symptoms. There is usually a progressive ascending
motor weakness starting in the lower limbs ranging from
difficulty in walking to paralysis. The weakness may
ascend to involve respiratory muscles and cause
respiratory failure. Facial nerve palsies are common and

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MFS
Miller Fisher syndrome (MFS) presents with ataxia,
areflexia and ophthalmoplegia. 25% of patients may
develop limb weakness. Electrophysiological studies
show primarily sensory conduction failure. Anti-
ganglioside antibodies to GQ1b are found in 90% of
patients and are associated with ophthalmoplegia. There
have been limited pathological studies in MFS but
demyelination of nerve roots has been demonstrated. A
critical difference between MFS and AIDP or acute
motor axonal neuropathy is the activation of anti-GQ1b
and anti-GT1a antibodies in MFS that target oculomotor
and bulbar nerves, which are nerves thought to have
relatively high GQ1b and GT1a ganglioside
densities(figure 3).[3]

Figure 2: Acute motor axonal neuropathy caused by

Campylobacter jejuni

Clinical features are similar to AIDP but tendon reflexes

may be preserved. Like AIDP, acute motor axonal
neuropathy is believed to be an IgG- and complement-
mediated disorder. Electrophysiological testing may
distinguish from other variants as selective motor nerve
and axonal involvement is demonstrated. In AMAN, the Figure 3: Antibody mediated axonal damage
pathological process involves binding of antibodies to
ganglioside antigens on the axon cell membrane, A chronic form of GBS known as chronic inflammatory
macrophage invasion, inflammation and axonal demyelinating polyneuropathy has been described. The
damage.[3] clinical features are similar to that of AIDP but have a
slowly progressive or relapsing course.[3,17]
AMSAN
Acute motor and sensory axonal neuropathy (AMSAN) INVESTIGATIONS[3]
is a variant of GBS in which both motor and sensory Serum biochemistry
fibers are involved and which can be demonstrated on Urea and electrolytes are usually normal but may have
electrophysiological studies. It is more severe and evidence of the syndrome of inappropriate ADH
associated with prolonged or even partial recovery. secretion (SIADH) or renal dysfunction. ALT and
Clinical features are similar to AMAN but also involve gamma GT may be raised in 33% of patients. Creatine
sensory symptoms. The underlying pathological process kinase may be raised.
is similar to that for AMAN (i.e. antibody mediated
axonal damage).[3] Inflammatory markers
Erythrocyte sedimentation rate is usually raised and C -
reactive protein is sometimes elevated.

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Tandel et al. European Journal of Pharmaceutical and Medical Research

Anti-ganglioside antibodies Other

Anti-GM1 is positive in 25% of patients and is Acute polymyositis
associated with a worse outcome. Anti-GD1a is Critical illness myopathy
associated with AMAN subtype of GBS. Anti-GQ1b is MANAGEMENT
associated with Miller-Fisher syndrome. Multi-disciplinary input is important in all aspects of the
care of patients with GBS both in the acute phase and
Infection screen rehabilitation of patients. Therapies may be classified as
Serology tests for Campylobacter jejuni, being supportive or immunomodulatory.
Cytomegalovirus, Epstein-Barr virus, Herpes simplex
virus, Mycoplasma pneumonia, HIV antibodies should Airway and Respiratory
be considered. Stool cultures looking for evidence of Around 30% of patients with GBS require ventilatory
gastrointestinal infections particularly Campylobacter support. Deterioration in respiratory function may be
jejuni. rapid and frequent assessments should be made in all
patients. Clinical markers suggestive of the need for
Radiological ventilatory support include bulbar weakness, inability to
A CT brain is indicated to exclude other causes of lift the head, upper limb weakness and tachypnoea.[2,3]
symptoms and evidence of raised intracranial pressure
prior to performing a lumbar puncture. An MRI of the Close monitoring of respiratory function tests is
spine may show selective anterior spinal nerve root imperative. Vital capacity should be measured three
enhancement with gadolinium and will exclude cervical times per day and can easily be assessed at the bedside.
nerve impingement. Measurement of vital capacity provides information
about respiratory sufficiency. Maximal inspiratory and
Lumbar puncture expiratory pressures may also be measured and provide
Increased protein levels and cell levels in CSF are information about the power of respective groups of
indicative of GBS respiratory muscles. Both tests may be difficult to
interpret in patients with bulbar weakness, due to
Nerve conduction studies difficulty forming a seal around the mouthpiece.
Findings depend on subtype of GBS. The majority show
demyelinating pattern while some patients may show Arterial blood gases may be measured to provide
evidence of axonal loss with little or no demyelination. objective evidence of the development of respiratory
failure. Oxygen saturations are easily monitored but de-
Respiratory function tests saturation can be a late sign.
These may show reduced vital capacity, maximal Clinical indications for intubation and ventilation
inspiratory and expiratory pressures. Arterial blood gases include:
may indicate progressive respiratory failure.
Vital capacity of less than 1L or less than 15 ml kg-.[1]
3,15,19
DIFFERENTIAL DIAGNOSIS Maximum inspiratory pressure of less than 30cm H 2O.
Neurological Maximum expiratory pressure of less than 40cm H 2O.
Myasthenia gravis Bulbar involvement with inability to cough, swallow and
Eaton-Lambert (myasthenic) syndrome protect the airway.
Multiple sclerosis Evidence of respiratory failure on arterial blood gases
Transverse myelitis and autonomic instability.[3]
Tracheostomy should be considered if prolonged
Metabolic respiratory support is likely to be needed. Respiratory
Hypokalaemic periodic paralysis physiotherapy can be invaluable in aiding the clearance
Hypermagnesaemia of secretions and prevention of hospital acquired
Hypophosphataemia pneumonias.
Acute intermittent porphyria
Anaesthetic considerations
Infective Suxamethonium is absolutely contraindicated in patients
Post diphtheria neuropathy with GBS. There have been a number of case reports of
Polio severe hyperkalaemia, life threatening arrhythmias, and
Botulism cardiac arrest after its administration.[4]
Tick paralysis
Cardiovascular
Drugs / toxins Autonomic dysfunction occurs in around 70% of patients
Heavy metal poisoning (e.g. lead) and may be life-threatening. Monitoring of the ECG,
Biological toxins (including snake and scorpion toxins) blood pressure and fluid balance is advisable. The most
Drugs (including stavudine, nitrofurantoin and common arrhythmia seen is sinus tachycardia but various
aminoglycosides) other ECG changes have been observed including atrial

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Tandel et al. European Journal of Pharmaceutical and Medical Research

and ventricular tachyarrhythmia, prolonged QT interval, Intravenous immunoglobulin

atrioventricular block and even asystole.[3] Intravenous immunoglobulin (IVIg) is an effective
treatment for GBS and has been demonstrated to be
Blood pressure may fluctuate between severe comparable to plasma exchange in accelerating recovery.
hypertension and hypotension. Orthostatic hypotension is It is most effective if administered within two weeks of
common. Care should be taken when treating extremes the onset of symptoms. IVIg has a number of advantages
of blood pressure with vasoactive drugs as patients may over plasma exchange. It is more widely available, less
be particularly sensitive to their effects. Intubated labour intensive and has less side effects. Indications for
patients with autonomic dysfunction may develop IVIg include muscle weakness and respiratory
instability after tracheal suction.3 depression.

Gastrointestinal IVIg contains pooled donor IgG antibodies and may

Good nutrition is important particularly for those patients reduce the severity of autoimmune inflammation in GBS
with bulbar weakness, and those who are sedated and by blocking Fc receptors. This prevents the Fc portion of
mechanically ventilated. Poor oral intake may necessitate antibodies binding and thus interrupts antibody mediated
instigation of enteral or parenteral feeding. Dietician cell destruction. Complement activation is also altered.
input is useful to ensure adequate calorific, Contraindications to IVIg include: previous anaphylactic
micronutrient, fluid and electrolyte intake. Patients with reaction to IVIg and IgA deficiency (associated with
autonomic dysfunction may be susceptible to the anaphylactic reactions to blood products). Side effects of
development of a paralytic ileus. This may be treated IVIg may be mild or severe and include nausea,
with prokinetic agents such as metoclopramide or headache, dermatological disorders including
erythromycin. erythroderma, fluid overload, deranged liver function
tests, venous thromboembolism, acute renal failure and
Neurological anaphylaxis. There is no evidence that repeated courses
Neuropathic pain is common and occurs in around 50% of treatment are beneficial.[3,9,16,18]
of patients. Non-opioid analgesics
(Paracetamol, NSAIDs) in combination with opioid Plasma exchange
analgesia should be instituted initially, but may provide Plasma exchange is an effective treatment and has been
inadequate pain relief. Adjunctive treatments such as shown to accelerate recovery in GBS.
anticonvulsants (e.g. gabapentin or carbemazepine), and
tricyclic antidepressants may be effective. Improvements have been demonstrated in regaining
muscle strength, ability to walk independently, and
Venous thromboembolism prophylaxis requirement for and duration of mechanical ventilation.
Immobile patients are at very high risk of deep vein It is more beneficial when commenced within one week
thrombosis and pulmonary emboli. Low molecular of the onset of symptoms, but can be beneficial up to
weight heparin in combination with either pneumatic thirty days after the onset of illness.[9]
compression devices or anti-embolism stockings, are
recommended until patients are able to walk unaided. Plasma exchange has been successfully used in mild,
moderate and severe cases of GBS with differing
Psychological numbers of exchanges depending on severity. The
There is a high incidence of depression among patients indications for plasma exchange are the same as for
with GBS. If available, it is important for the patient and IVIg. Plasma exchange involves the passage of blood
their family to have access to support groups. It is also through an extracorporeal cell separator. The plasma
important that counseling and psychiatric help be fraction of the blood is removed and replaced with FFP
available if needed.[3] or human albumin solution. Anticoagulants are
administered during the procedure. The aim of plasma
Rehabilitation exchange is to remove antibodies associated with the
40% of patients who suffer from GBS will need underlying autoimmune response. Contraindications to
admission for inpatient rehabilitation. Careful attention plasma exchange include: coagulopathy, overwhelming
should be paid to limb positioning and posture as limb sepsis, haemodynamic instability and shock. Side effects
weakness can lead to compression nerve palsies, pressure vary from mild to more severe and include nausea,
sores and contractures. Extensive input from vomiting, diarrhoea, fevers, coagulopathy,
physiotherapists and occupational therapists is essential immunosuppression, hypocalcaemia which relates to the
to provide tailored strengthening exercises and use of citrate and line related complications.[3,7,8]
supportive aids. Patients may also suffer from persistent
fatigue, which may respond to an exercise Corticosteroids
programme.[3,5] Corticosteroids have been used historically, in order to
suppress inflammation associated with Guillain- Barr
syndrome. They are now no longer used. There is no

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Tandel et al. European Journal of Pharmaceutical and Medical Research

evidence that they improve recovery or affect long-term Royal Society of Tropical Medicine and Hygiene,
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