US Pharm. 2014;39(1):35-38.
ABSTRACT: Guillain-Barré syndrome is a
heterogeneous condition with several variant forms that is the most
common cause of acute flaccid paralysis in both children and adults. It
is estimated that the condition affects about 1 to 3 individuals per
100,000 persons. Patients typically complain of increasing pain and
weakness in the limbs associated with tingling dysesthesias in the
extremities. The majority of patients with Guillain-Barré have been
diagnosed with an infection in the 3 weeks prior to the development of
symptoms. Other events that have been linked to the disorder include
vaccinations, surgery, and certain drugs. Therapy includes immunotherapy
to accelerate the recovery process as well as specific therapies for
individual patients such as pain relief.
Guillain-Barré syndrome (GBS) is a heterogeneous condition associated with immune-mediated, reactive, self-limiting peripheral neuropathies.1,2
It represents at least five different entities that are associated with
an increased concentration of cerebrospinal fluid protein but a normal
cell count and manifest as systemic motor paralysis.1,2
Three of these forms predominantly affect the motor
system: acute motor axonal neuropathy (AMAN), acute motor-sensory axonal
neuropathy (AMSAN), and acute inflammatory demyelinating
polyradiculoneuropathy (AIDP).1 The other two variants are Miller Fisher syndrome and acute pandysautonomic neuropathy.1
GBS is the leading cause of flaccid paralysis in Western
countries. It is estimated that direct healthcare costs of patients in
the United States alone amount to $110,000 per person, and costs due to a
loss in productivity per patient run close to $360,000 annually.2,3
The disorder, triggered by a preceding bacterial or viral
infection, causes respiratory failure requiring mechanical ventilation
in approximately 25% of cases.2 Mortality rates in patients
requiring mechanical ventilation are as high as 20%, with persistent
disability and persistent fatigue in 20% and 67% of patients,
Since there is no reference test that would allow for a
positive confirmation of the diagnosis of GBS, it has been difficult to
establish accurate epidemiologic data. GBS affects between 1 to 3
individuals per 100,000 persons, with males being 1.5 times more likely
to be affected.5 The condition has been reported worldwide in all age groups, with the incidence increasing linearly with age.2,5
The peak incidences occur at late adolescence and in the elderly. It is
thought that the bimodal peaks are possibly related to the increased
risk of cytomegalovirus and Campylobacter jejuni in the former
group and failing immune suppressor mechanisms in the latter population.
The annual incidence in patients over age 70 years increases to 8.6 in
100,000 people. Pregnant women are at a lower risk of developing GBS;
however, their risk increases immediately after delivery.2
GBS is characterized by rapidly evolving symmetrical limb weakness that accompanies tingling dysesthesias in the extremities.2
The weakness is more prominent in proximal muscles, with the lower
limbs being more affected than the upper limbs. The paresthesias spread
proximally, but rarely pass the wrists and ankles. The patient’s eye
movements, swallowing movements, facial muscles, and airway maintenance
may be disrupted if his or her cranial nerve is affected.2 The symptoms of the syndrome can be divided into three phases6:
1.The progressive phase, which lasts a few days to 4 weeks
2. The plateau phase, which consists of persistent symptoms and lasts for a few days or weeks
3. The improvement phase, when recovery takes place.
About half of patients with GBS complain of severe pain
that is experienced with the slightest of movements. The most common
sites of pain are the shoulder, girdle, back, and posterior thighs.7,8 The pain can be neuropathic as well as nociceptive in origin.9
Etiology and Pathogenesis
Antecedent events are implicated in the pathogenesis of GBS. TABLE 1 lists some of the identified events that lead to GBS.2,10
More than 60% of patients who are diagnosed with GBS have
been diagnosed with an infection in the 3 weeks prior to the onset of
weakness. The most common antecedent symptoms have been fever, cough,
sore throat, and nasal discharge.5
GBS is a generalized peripheral disorder that can be confused with several other conditions.7,11
The diagnosis is based upon the typical clinical features, an
electrodiagnostic examination, and examination of the cerebrospinal
fluid. It is useful to determine the specific subtype that the patient
is suffering from since the axonal forms (AMAN and AMSAN) tend to have a
The only clinical feature that is required for the diagnosis of GBS is progressive weakness in both arms and both legs.2
The progression of the typical symptoms over days to 4 weeks, the
relative symmetry of the symptoms, the presence of mild sensory
symptoms, and symptoms indicative of cranial nerve involvement and/or
autonomic dysfunction strongly support the diagnosis of GBS.2
If a diagnosis of botulism, myasthenia, poliomyelitis, or
toxic neuropathy is made; if abnormal porphyrin metabolism is noted; if
there is a history of recent diphtheria; or if a purely sensory syndrome
without weakness is observed, then GBS can possibly be ruled out.2 There are distinct features of the various types of GBS; these are listed in TABLE 2.17-20
The overall treatment is the same for all GBS variants.
Since the disease can be fatal, optimal care is provided in a hospital
setting with intensive care facilities. Excellent multidisciplinary care
involving supportive care as well as specific therapy is needed to
manage the disease.20
Immunotherapy: Immunotherapy has been
shown to accelerate recovery in patients with GBS, particularly when
initiated early after motor symptoms appear. However, it is unnecessary
in mild cases where no motor symptoms are exhibited. There are two forms
of immunotherapy indicated for specific therapy of GBS, plasma exchange
and intravenous immunoglobulin G (IVIG).1
Plasma exchange is a process that removes or dilutes the circulating immune factors implicated in the pathogenesis of GBS.5
This procedure has been shown to reduce the need for mechanical
ventilation and hospitalization time by hastening recovery in
nonambulant patients who seek treatment within 4 weeks of the onset of
neuropathic symptoms. The maximal benefit therapy is seen if it is
initiated within the first 2 weeks of onset. The usual regimen of plasma
exchange is 5 times over 2 weeks, with a total exchange of about 5
plasma volumes. The disadvantages of plasma exchange include rare
complications, such as sepsis. Furthermore, the use of fresh frozen
plasma is associated with the risk of acquiring viral infections such as
IVIG, which is easier to administer than plasmapheresis,
is associated with fewer complications and is more comfortable for the
patient.5,21 It is recommended for patients who cannot ambulate without assistance within 2 or 4 weeks of neuropathic symptom onset.4,22 The recommended dose is 0.4 g/kg per body weight daily for 5 consecutive days.5 As an added advantage, the patient’s CD8+ T-cell function is enhanced by an unknown function by the use of IVIG.23
Patients on IVIG may develop self-limiting, influenza-like symptoms including fever, myalgia, headache, nausea, and vomiting.1,23
Other side effects include aseptic meningitis, neutropenia, and
hypertension. Caution must be used when administering IVIG to patients
with congestive heart failure and renal insufficiency, and its use is
contraindicated in those patients with a previous history of anaphylaxis
to IVIG. The risk of serious hepatitis C infection transmission has
been reduced significantly, following changes in preparation and
Corticosteroids: While oral
corticosteroids and IV methylprednisolone were once believed to be
useful in the treatment of GBS due to their immune-mediated inflammatory
mechanism, they are no longer used because they do not seem to offer
any benefit over immunotherapy. Furthermore, there seems to be no added
advantage of adding corticosteroids to an IVIG regimen.4
Even though immunotherapy has almost halved the duration
of mechanical ventilation, about 25% of all patients with GBS
demonstrate respiratory failure requiring ICU admission and invasive
mechanical ventilation.20,24 Respiratory failure tends to be
more likely in cases with rapid progression, bulbar palsy, upper limb
involvement, and autonomic dysfunction.20 Endotracheal
intubation and mechanical ventilation should be initiated within 24
hours of symptom onset in an ICU together with regular monitoring and
measurement of vital capacity. These steps form an essential part of
therapy since a positive clinical outcome largely depends upon the
anticipation and management of ventilatory failure and its
Pain remains an undertreated but important aspect of GBS.
Furthermore, patients who are immobilized and require tracheal
intubation are not able to effectively express the extent of pain
experienced. A pain management regimen should therefore be considered in
all patients presenting with GBS.
While opioids and NSAIDs have traditionally been used in
pain management plans, their host of side effects has prompted the
development of safer therapeutic modalities. Opioids, while providing
effective pain relief, have been linked to tolerance, dependence,
respiratory depression, sedation, and constipation.9 Furthermore, they should be used with caution since there is an already present risk of ileus in patients with GBS.9,26 On the other hand, NSAIDs can lead to ulceration, bleeding, platelet dysfunction, and renal and hepatic failure.9
Anticonvulsants are frequently used in the management of
neuropathic pain associated with GBS. Small trials have shown a positive
analgesic effect with gabapentin or carbamazepine for pain management
in GBS.27 The typical dosages used for pain management are
900 to 3,600 mg of gabapentin or 100 to 1,200 mg of carbamazepine
administered as three divided doses.28
Physical therapy involving gentle massage, passive range
of motion exercises, and frequent position changes may provide adjuvant
relief in some patients. This may be integrated together with a
rehabilitation program including occupational and physical therapy to
overcome the persistent fatigue that is experienced due to the loss of
About two-thirds of patients with GBS experience
cardiovascular complications and need to be managed appropriately. These
changes, attributable to autonomic neuropathy, include heart rhythm
abnormalities, blood pressure variability (both hypo- and hypertension),
myocardial involvement, acute coronary syndromes, and
Patients with severe disease should be monitored for
cardiac arrhythmia. Nonambulant adult patients are at a risk of venous
thromboembolism, usually occurring between 1 to 10 weeks following the
onset of symptoms.27 Subcutaneous low-molecular-weight
heparin (LMWH) and graduated compression stockings may be initiated as
prophylactic therapy against deep venous thrombosis.20
Future research needs to be focused on developing accurate
diagnostic methods as well as protocols to identify at-risk patients.
The role of immunotherapy in patients with GBS needs to be fully
established, and effective therapies are yet to be developed.4
IV eculizumab, interferon beta, and mycophenolate mofetil are all
currently undergoing investigation for use in the management of GBS.27 Other areas of research include investigating ventilator support measures and management of fatigue.4
Pharmacists have an important role to play in providing guidance on the
correct use of existing therapies as well as supportive measures.
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