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- 1. JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 19
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G
uillain-Barré syndrome (GBS) is an acute general-
ized polyneuropathy affecting 1 to 2 out of
100,000 people per year. More men than women
are affected (1.25:1), and the syndrome may occur in
patients of any age, typically affecting patients ages 40
to 50 years, although incidence is increased by 20% for
every 10-year increase in age.1
GBS can be classified into three main subtypes:
• Acute inflammatory demyelinating polyneuropathy, the
most common type and the focus of this article
• Axonal, acute motor axonal neuropathy and acute motor
sensory axonal neuropathy
• Miller Fisher syndrome.
Symptoms of acute inflammatory demyelinating polyneu-
ropathy evolve rapidly, and are characterized by progressive
ascending weakness and diminished or absent deep tendon
reflexes.2
The degree of weakness varies from minimal dif-
ficulty walking to complete paralysis including the facial,
respiratory, and bulbar (tongue and swallowing) muscles.
CAUSES
GBS usually develops after a triggering event.
Infections Campylobacter jejuni, one of the most com-
mon causes of gastroenteritis worldwide, causes 30% to
35% of GBS cases.3
Other infectious triggers include
cytomegalovirus, Mycoplasma pneumoniae, Haemophilus
influenzae, Epstein-Barr virus, and HIV. GBS also occurs
in patients with lymphoma, Hodgkin disease, and systemic
Robert Estridge practices at the Cleveland Clinic in Cleveland, Ohio.
Mariana Iskander is a hospitalist in the Neurological Institute at the
Cleveland Clinic in Cleveland, Ohio. The authors have disclosed no
potential conflicts of interest, financial or otherwise.
DOI: 10.1097/01.JAA.0000466585.10595.f5
Copyright © 2015 American Academy of Physician Assistants
Understanding Guillain-Barré syndrome
Robert Estridge, PA-C; Mariana Iskander, PA-C
ABSTRACT
Guillain-Barré syndrome (GBS) is a rapidly progressive
peripheral neuropathy that most commonly presents with
ascending symmetrical weakness and diminished or absent
deep tendon reflexes. Because weakness may affect the
diaphragm and cause respiratory distress, 10% to 30% of
patients require mechanical ventilation. Symptoms prog-
ress and peak about 4 weeks after onset. Patients generally
require hospitalization for respiratory and cardiac monitor-
ing, as well as supportive care and treatment. The treat-
ments of choice are IV immunoglobulin and plasmapheresis.
Even after treatment, as many as 20% of patients have
persistent neurologic symptoms, and up to 3% of patients
die of autonomic issues.
Keywords: Guillain-Barré syndrome, polyneuropathy,
plasmapheresis, Campylobacter jejuni, IVIG, autonomic
dysfunction
Learning objectives
List the pathophysiology, signs, and symptoms of GBS.
Describe the important aspects of diagnosis and management
of patients with GBS.
FIGURE 1. An oligodendrocyte repairing damaged myelin
sheaths of a motor neuron
©CAROL&MIKEWERNER/VISUALSUNLIMITED,INC.
Copyright © 2015 American Academy of Physician Assistants
- 2. 20 www.JAAPA.com Volume 28 • Number 7 • July 2015
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lupus erythematosus; these cases occur more frequently
than can be attributed to chance alone.3
Other causes A small percentage of patients develop GBS
after another triggering event such as immunization,
surgery, trauma, or bone marrow transplantation. One
study based on a vaccine used in the 1970s found that the
H1N1 influenza vaccine increased the risk of developing
GBS in 2 per 1 million people vaccinated.4
PATHOPHYSIOLOGY
GBS appears to be an autoimmune response in which the
immune system attacks the peripheral nervous system.
Infections such as C. jejuni express lipooligosaccharides
in the bacterial wall; these molecules are similar to gan-
gliosides, and antiganglioside antibodies produced by the
body attack the nerve and destroy the myelin sheath.
Exactly which antibodies are stimulated and which area
of the nerve is targeted may explain the different subtypes
of GBS.4
SIGNS AND SYMPTOMS
The most prominent symptom experienced by patients
with GBS is bilateral, ascending, symmetrical weakness of
the limbs. In 90% of patients, weakness starts in the legs
and advances proximally. Between 10% and 30% of
patients require mechanical ventilation secondary to
respiratory muscle weakness.5
Between 50% and 89%
of patients report pain in addition to weakness, especially
with movement. Pain is described as severe, deep aching
or cramping in the back or legs. It is often worse at night
and may be difficult to control.6
Weakness typically peaks at 2 weeks for 50% of patients,
and by 4 weeks for 90% of patients.7
Weakness is consid-
ered a significant factor in the diagnosis of GBS. The
patient’s reflexes are diminished to absent.
Autonomic symptoms affect 70% of patients, most com-
monly causing cardiac dysrhythmias, but also causing BP
instability. Other autonomic symptoms include paralytic
ileus, abnormal sweating, orthostasis, and urinary reten-
tion.8,9
Facial diparesis occurs in 50% of patients. The
lower cranial nerves also are frequently involved, causing
bulbar weakness that makes it difficult for patients to
manage secretions and maintain an airway; these patients
may initially be thought to have brainstem ischemia.3
Monitor patients with GBS closely for signs of respira-
tory failure, and perform frequent bedside measurements
of vital capacity and negative inspiratory force. Signs of
impending respiratory arrest and the need for endotracheal
intubation are:
• Forced vital capacity less than 20 mL/kg
• Maximum inspiratory pressure less than 30 cm H2
O
• Maximum expiratory pressure less than 40 cm H2
O or
a reduction of more than 30% in vital capacity.10
DIAGNOSIS
The differential diagnosis of GBS includes acute myelopa-
thy, arsenic poisoning, botulism, cytomegalovirus, critical
illness neuropathy or myopathy, diphtheria, Lyme polyra-
diculitis, myasthenia gravis, organophosphate or paralytic
shellfish poisoning, poliomyelitis, porphyria, severe hypo-
phosphatemia, thallium poisoning, vasculitis neuropathy,
and West Nile virus.
Diagnostic criteria for GBS are listed in Table 1. Patients
with GBS classically have elevated protein levels (as high
as 1,800 mg/dL compared with the normal range of 15 to
45 mg/dL) and normal white blood cell (WBC) counts in
the cerebrospinal fluid (CSF), a condition known as albu-
minocytologic dissociation.3
Protein levels in the CSF may
be normal in early GBS; however, by the end of the second
week of symptoms, protein levels in the CSF are elevated
in 90% of patients.4
One study of 474 patients found
higher-than-normal CSF protein concentrations in 49%
of patients on the first day and 53% of patients in the first
3 days.11
This percentage typically increases as the syndrome
progresses, so clinicians should not rely solely on elevated
protein levels in the CSF for diagnosis, especially early in
the course of GBS.
Interestingly, MRI of the lumbosacral spine, which can
be used to rule out other diagnoses, may reveal gadolinium
enhancement of the lumbosacral nerve roots, aiding the
diagnosis of GBS.12
TREATMENT
Treatment typically focuses on supportive care and mon-
itoring the patient’s respiratory, cardiac, and electrolyte
status.
Supportive care The following recommendations are in
agreement with a 2005 expert review of supportive care
for patients with GBS, and are based on observational
studies and expert opinion:
• Immunizations are not recommended during the acute
phase of GBS and are not suggested for a period of 1 year
or more after the onset of GBS.
• After 1 year, immunizations need not be withheld, but
the need for the immunization should be reviewed on an
individual basis.10
Key points
GBS is an acute inflammatory demyelinating poly-
neuropathy characterized by motor difficulty, diminished to
absent reflexes, and possible cranial nerve involvement.
In 70% of patients, GBS develops after an infection, most
commonly C. jejuni.
Diagnostic testing shows increased CSF protein.
Respiratory difficulties or cardiac dysrhythmias require
patients to be hospitalized for supportive care.
Treatment with IVIG or plasmapheresis can improve
symptoms.
Copyright © 2015 American Academy of Physician Assistants
- 3. Understanding Guillain-Barré syndrome
JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 21
Annual influenza vaccination is considered beneficial for
most patients who have a history of GBS that is not pro-
voked by influenza vaccination, and who have risk factors
for severe influenza complications (for example, older age
or immunosuppression).
The two main treatments for GBS are plasma exchange
(PLEX) and IV immunoglobulin (IVIG).
PLEX First described as a treatment for GBS more than
30 years ago, PLEX filters pathogenic substances from the
blood and removes the offending antibodies behind the
pathophysiology of neural destruction. PLEX also can be
used to treat antiphospholipid antibody syndrome, mul-
tiple sclerosis, myasthenia gravis, neuromyelitis optica,
and rhabdomyolysis.
Long-term effects of PLEX include immunosuppression
and transfusion reactions. Some immediate adverse reac-
tions include symptoms associated with hypocalcemia (seen
in about 20% of patients), as well as allergic reactions
including urticaria or pruritus.13
Treatment with PLEX has significantly reduced patients’
need for mechanical ventilation from 27% to 14%.2
PLEX
also has increased the rate of recovery and reduced the
need for ambulatory assistive devices. Five PLEX treatments
are typical for patients with GBS.2
IVIG This treatment began more than 50 years ago when
pooled human plasma was used to treat measles and
hepatitis. Since then, clinicians have used IVIG to treat
Kawasaki disease, idiopathic thrombocytopenic purpura,
and chronic inflammatory demyelinating polyneuropathy.14
IVIG is thought to have multiple mechanisms of action,
which are not totally understood. One theory proposes
that IVIG provides an antigen that blocks autoantibodies
from binding to B lymphocytes. IVIG’s multiple other
mechanisms are related to T-cells (reducing the production
of interleukin), and complement system (antibodies against
C3 and C4), and will not be discussed in detail here.15
IVIG protects patients against infection and suppresses
inflammatory and immune-mediated processes. The stan-
dard dose is 0.4 g/kg/day for 5 days. This procedure is
most beneficial if started within 2 weeks of symptom onset,
although it has been shown to be beneficial if started within
4 weeks of symptom onset.4
Trials analyzing the efficacy of IVIG versus PLEX have
concluded that they are of equivalent efficacy.10
Due to the
incidence of adverse reactions to PLEX, IVIG has become
more widely used as a first-line treatment for GBS.4,7
Other treatments Corticosteroids have not been shown
to be helpful, but rather, have been shown to delay recov-
ery from GBS, although they are used when the symptoms
become chronic.16
Sodium channel blockers are being studied for the treat-
ment of GBS. These drugs may significantly protect nerve
axons from damage.2
PROGNOSIS
About 85% of patients with GBS achieve a full recovery
within several months to a year. Fatigue is the most com-
mon and persistent symptom after treatment.5
Other less-
common residual difficulties include weakness of the lower
leg muscles, numbness of the feet and toes, and mild
bifacial weakness.
Five percent to 10% of patients who improved with
treatment will have a relapse within 3 days to 3 weeks after
completing treatment. If the patient responded to the
initial therapy, the same treatment may be used, or an
alternative treatment may be tried; either can be successful
(for example, PLEX or IVIG).12
Even with treatment,
however, 3% to 5% of patients with GBS die, most often
from cardiac arrest related to autonomic dysfunction, acute
respiratory distress syndrome, pulmonary embolism, or
infection.12
CONCLUSION
GBS typically causes acute, rapid, and progressive ascend-
ing motor weakness. Early recognition and treatment are
crucial, especially for patients who need mechanical ven-
tilation. Most patients are admitted to the hospital for
cardiac and respiratory monitoring.
The two therapeutic options for GBS that have been
shown to be the most effective in improving symptoms are
IVIG and PLEX. Most patients exhibit near-full functional
recovery in about a year, with occasional residual difficul-
ties. The syndrome has a 3% to 5% mortality. Reviewing
the possible progression of disease and prognosis are keys
to the family discussion, and are crucial to setting appro-
priate expectations. JAAPA
Required:
• Progressive weakness in both arms and legs
• Areflexia
Strongly support:
• Symptom progression over days and for up to 4 weeks
• Relative symmetry of symptoms
• Mild sensory symptoms or signs
• Cranial nerve involvement, especially bilateral weakness
of facial muscles
• Recovery beginning 2 to 4 weeks after symptom progres-
sion ceases
• Autonomic dysfunction
• Absence of fever at onset
• High concentration of protein in CSF
• Typical electrodiagnostic features
Rule out GBS:
• Diagnosis of botulism, myasthenia, poliomyelitis, or toxic
neuropathy
• Abnormal porphyrin metabolism
• Recent diphtheria
• Purely sensory syndrome, without weakness
TABLE 1. Diagnostic criteria for GBS17
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