A Case of Guillain-Barre Syndrome in a Primary Care Setting

A Case of Guillain-Barre Syndrome
in a Primary Care Setting
Sherly Sebastian, DNP, RN, NP-C
ABSTRACT
Guillain-Barre Syndrome (GBS) is an immune-mediated peripheral neuropathy
characterized by rapidly progressive symmetrical ascending weakness and sensoiy
loss. The disease can progress rapidly and be fatal i f diagnosis and treatment interventions are delayed. I n most patients, the neuropathic symptoms are preceded by an
antecedent infection. The patient may present w i t h initial symptoms o f upper respiratory tract infection or gastroenteritis. This article presents a case report o f GBS, followed by a detailed discussion o f the pathophysiology, diagnostic studies, differential
diagnosis, types, prognosis, and management o f patients w i t h this condition.
Keywords: ascending weakness, immune response, peripheral neuropathy,
respiratory failure, sensory loss
© 2012 American College of Nurse Practitioners
G
uillain-Barre Syndrome (GBS) is an i m m u n e -
ness, tingling, and weakness in her legs. The patient was
mediated peripheral neuropathy characterized
initially seen in the clinic 3 weeks ago w i t h upper respi-
by rapidly progressive symmetrical ascending
ratory tract infection and was treated w i t h a course o f
weakness and sensory loss. The disease is named after the
amoxicillin. Her upper respiratory symptoms improved,
physicians Guillain, Barre, and Strohl, w h o described the
but a week later she noticed numbness and tingling in
clinical presentation in 2 French soldiers during the First
her feet, progressively ascending to her legs and thighs.
World War about 100 years ago.' According to the
She was evaluated at the local hospital, and her diagnostic
National Institute o f Neurological Disorders and Stroke
work-up included blood cultures and spinal tap.The
figures,' the annual incidence rate for GBS is about 1-2
emergency r o o m (ER) physician consulted the neurolo-
per population o f 100,000. I n the acute phase o f GBS,
gist, but the patient left E R against medical advice.
approximately 3% o f patients may die from acute c o m p l i -
^ T h e numbness became progressively worse, and she
cations and up to 20% have residual, permanent, severe
started having bilateral lower extremity weakness and gait
disabilit)' w i t h ambulation deficits or require ventilator
issues. She fell 2 days ago, and her family forced her to
assistance up to 12 months later,-'
seek medical help. Her past medical history was unre-
The annual financial burden from GBS is estimated at
$1.7 bilhon, including 10.2 bilhon (14%) in direct med-
markable except for the upper respiratory infection
( U R I ) 3 weeks ago. The patient's review o f systems was
ical costs and $1.5 billion (86%) in indirect costs from
negative for shortness o f breath, fever, chilis, cough, and
lost productivity or premature death.** Even though inci-
swallowing difficulties. H e r vital signs were temperature
dence is low, the economic cost o f GBS is substantial as a
3 7 ° C , pulse 112/minute, blood pressure 108/62, respira-
result o f high mortahty and morbidity.
tion 28/minute, weight 162 lbs, height 5'2".
CASE REPORT
oriented X 3, w i t h intact speech, comprehension, and mem-
This patient is a 36-year-old Hispanic woman w h o pre-
017; pupils equal round reactive to light. Dysmetria was
sented to the outpatient clinic w i t h complaints o f numb-
noted for finger-to-nose and rapid alternating movements
O n neurological examination, the patient was alert and
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643
Table 1. Guillain-Barre Syndrome Variants
Acute Inflammatoty Demyelinating Polyneuropathy (AIDP)^'
Most prevalent in United States and Europe
Immune response at myelin sheath and Schwann cells
Cranial and sensory nerves more affected than motor
nerves
Acute Motor Axonal Neuropathy (AMAN)
More prevalent in pediatric group
Immune response is against motor axon membranes
Motor involvement without sensory findings
Acute Motor and Sensor Axonal Neuropathy (AMSAN)
More rapid progression and paralysis with sensory and
motor deficits
Axonal degeneration of ventral and dorsal nerve roots
Prolonged recovery with painful sensory component
Miller-Fisher Syndrome (MFS)
Rare subtype, classic findings of areflexia, ataxia, and
ophthalmoplegia
Acute Panautonomic Neuropathy
Very rare subtype affecting both sympathetic and
parasympathetic systems
Recovery is slow and incomplete, with high mortality
and morbidity
Table 2. Clinical Manifestations^"
A. Clinical symptoms definitive of GBS
Bilateral symmetrical ascending motor weakness,
areflexia
B. Clinical symptoms supportive of GBS
Ataxia, cranial nerve palsies
Respiratory muscle weakness and paralysis
Numbness/paresthesia on extremities
Decreased proprioception
Pain in the lower extremities and back, fatigue
Bilateral facial weakness, difficulty with eye
movements
Chewing and swallowing difficulties
Autonomic dysfunction
C. Clinical symptoms not supportive of GBS
Unilateral weakness, hyperreflexia
Sudden onset of weakness
Changes in level of consciousness
Asymmetry of weakness and paresthesia
Severe paresthesia without motor weakness
Severe respiratory symptoms with limited motor
weakness
Bladder or bowel dysfunction at the onset of
symptoms
bilaterally. Her cranial nerve exam was intact. Her motor
peripheral myelin sheath. The commonly recognized
strength in triceps, biceps, and supinator were 5/5; deltoids
variants are summarized i n Table 1.
and pronator were 4/5; wrist extensors and flexors were
The patient in the case study provides many o f the
4/5 bilaterally; hip flexors, quadriceps, and hamstrings
classic characteristics o f GBS, such as progressive
were 4/5 bilaterally; dorsiflexors and plantar flexors were
development o f ascending symmetrical paresthesia,
3/5 bilaterally. Her sensation was intact on upper extremities
pain, bilateral m o t o r weakness, areflexia, and ataxia.
but diminished to touch and pin prick on lower extremities
Accurate diagnosis requires clues from the clinical his-
and abdomen. Her gait was ataxic, deep tendon reflex
tory, such as onset, severity', and rate o f progression o f
( D T R ) 1 + and symmetrical on deltoid, biceps, brachio-
the symptoms over hours to days. A careful n e u r o l o g i -
radialis and triceps; D T R was absent on knees and ankles.
cal exammation m c l u d i n g the m o t o r strength, cranial
The patient's laboratory studies did not reveal any
infectious process. H e r cerebrospinal fluid (CSF) studies
nerves, and reflexes is essential. Clinical manifestations
are summarized i n Table 2.
from the hospital revealed elevated protein count o f
200 m g / d L , w i t h normal cell count, w h i c h confirmed
Antecedent Infections
the diagnosis o f GBS. The disease can progress rapidly
The history o f a prodromal respiratory infection should
and can be potentially fatal i f treatment interventions are
raise suspicion for GBS, because in majority o f GBS
delayed. The patient was transported expeditiously to the
patients, neuropathic symptoms are preceded w i t h a U R l
nearest hospital for admission to the intensive care unit.
or enteric infection. History o f cough, fever, sore throat,
diarrhea, or any other types o f infections 2-3 weeks
DIAGNOSIS
before the onset o f weakness should alert the clinician to
GBS is a heterogeneous syndrome w i t h several variant
suspect GBS. Campylobacter jejuni, a bacteria commonly
forms affecting the peripheral nervous system as a result
associated w i t h gastroenteritis, have been identified as the
o f an immune-mediated disturbance involving the
most frequent antecedent pathogen o f GBS.'
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Volume 8, Issue 8, September 2012
Vaccinations
The evolution o f GBS after vaccination has been studied
Table 3. Differential Diagnoses^^'^"
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
extensively, as concerns about vaccine-induced GBS were
S y m p t o m s similar t o GBS but progressing over a longer
initially raised after the 1976-77 influenza vaccination
period ( > 8 weeks)
period.The landmark study done by Lasky et al '
reported marginally increased risk o f GBS after influenza
vaccination during the first 6 weeks o f immunization.
Subsequently, researchers investigated the relationship
between GBS and the influenza vaccinations and
reported that low relative risks were not statistically significant.'"Extensive research is reported after the H l N l
mass vaccination i n 2009 and found no evidence o f an
increased risk o f GBS after the seasonal influenza vaccine
or the H l N l vaccination."
Myasthenia Gravis (MG)
Weakness in t h e v o l u n t a r y muscles c o n t r o l l i n g t h e
eyelids, face, s w a l l o w i n g
Weakness and fatigue p r o n o u n c e d w i t h effort and
relieved w i t h rest
Diplopia and/or ptosis, n o r m a l sensation and reflexes
Anterior Horn Cell Abnormalities
S o m e similar features, but weakness pattern is different
Clinical signs of infection, i n c l u d i n g high cell count in
cerebrospinal fluid
Spinal Cord Disorders
Radiculopathy, unilateral m o t o r and sensory deficits
Diagnostic Studies
Hyperreflexia, sharp sensory levels
CSF analysis w i t h evidence o f high protein and normal
Pain aggravated w i t h activities
cell count support the diagnosis o f GBS. The value o f
lumbar puncture is limited i n the early phase o f the disease. CSF may remain normal in up to 50% o f patients
Intracranial Abnormalities
Change In level o f consciousness, severe headaches
Unilateral m o t o r and sensory deficits
early i n the disease, but elevated protein w i l l be present
i n more than 90% o f the patients by the time they reach
clinical nadir.'* However, increased CSF ceD count steers
to make the diagnosis on clinical grounds and promptly
cUnician to consider other diagnoses and investigate pos-
refer to hospital/specialist care.*^''-*
sibility o f infectious process, such as leptomeningeal
malignancy. West N i l e virus infection, HIV, or Lyme dis-
Differential Diagnosis
ease.'- I f the CSF results are normal, repeat testing is not
Ascending symmetrical weakness progressing over hours
done typically.
to days is the cardinal symptom o f GBS. I f the symptoms
Electrodiagnostic testing is done frequently to iden-
are prolonged over 8 weeks, other diagnoses should be
tify the acute motor weakness caused by a peripheral
considered. I f the weakness is asymmetric, clinicians
neuropathy. T h e test is helpful i n confirming the diagno-
should consider a spinal or intracranial diagnosis instead
sis and differentiating the variants o f GBS. However,
o f GBS. I f there is weakness w i t h intact reflexes, another
early in the disease process, the testing may be normal.
diagnosis should be investigated. The predominant fea-
The features o f deniyelination i n GBS include slow con-
tures o f Miller Fisher Syndrome, such as ophthalmo-
duction, temporal dispersion, and prolonged or absent
plegia, areflexia, and ataxia, often mistakenly suggest
F-responses.^ Abnormal median and ulnar sensory
brain stem infarction. A wide range o f neurological disor-
potentials w i t h spared sural potentials are seen i n the
ders may mimic the symptoms o f GBS; most comnion
initial stages o f GBS.'•'The nerve conduction study is
differentials are hsted i n Table 3.
considered a useful confirmatory test, w h i c h typically
demonstrates the finding o f reduced muscle action
PATHOPHYSIOLOGY
potentials in chnically weak m u s c l e s . M a g n e t i c reso-
The pathogenesis o f GBS has been widely studied but is
nance imaging ( M R I ) is typically performed to rule out
still not completely understood.The proposed mecha-
infiltrative or structural causes o f weakness. Moreover,
nism involves an antecedent infection leading to an auto-
M R I may reveal enhancement o f the affected nerve
immune response reacting w i t h peripheral nerve
roots supportive o f GBS diagnosis. The hmitations o f
components (Figure 1). Most o f the pathogens gains
these tests i n the early phase o f the disease, combined
entry to the body through mucosal or gut epithehum
w i t h the urgency for early treatment, require clinicians
and induce antibody production against specific ganglio-
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645
JNP
r
Figure 1. Guillain-Barre Syndrome Pathogenesis.
Disease-modifying factors
Pathogenesis and recovery
Bacterial factors
• LOS biosynthesis cluster
• Ganglioside mimicry of LOS
Campylobacterjejuni infection
Tcell
Host factors
• Genetic polymorphisms
• Immune status
Immune response to LOS
Antigen
presenting
cell
Plasma cell
Cross-reactive antibodies
to nerve gangliosides
^ k h
Macrophage
Extent of nerve damage
• Ganglioside distribution in nerves
• Specificity/affinity antibodies
• Complement activation
Nerve dysfunction
Complement
Conduction dysfunction/block
I
X
Clinical prognostic factors
-Age
• Severity at onset
' Diarrhoea
Outcome
van Doom PA, Ruts L, Jacobs
2008;7:939-950.
646
BC. Clinical features, patfiogenesis,
Reprinted with permission
from
The Journal for Nurse Practitioners - JNP
and treatment of Guillain-Barre Syndrome.
Lancet Neurol.
Elsevier.
Volume 8, Issue 8, September 2012
sides i n myelin/' The immune response depends on bac-
Table 4. Autonomic Dysfunction^'^^
terial factors, such as the specificity o f lipo-ohgosaccha-
Tachycardia, bradycardia
ride (LOS), and on host factors, such as genetic
Hypotension, hypertension
polymorphism and immune status.'"The presence o f
antibodies leads to activation o f T cells and complements,
leading to a cascade o f inflammation and demyelination.
Facial flushing, anhidrosis, hyperhidrosis
Constipation, paralytic ileus
The demyelination decreases the velocity o f nerve conduction and slows the impulse transmission along the
exchange o f about 5 plasma volumes. The Cochrane
axons. The extent o f nerve damage varies, w i t h more
Review'^ demonstrated that I V I g and PE are beneficial
damage seen in the intensely myelinated peripheral
for accelerating the recovery o f GBS, i f given during the
nerves, causing motor and sensory weakness.
first 4 weeks o f the disease, w i t h most benefit seen i f
The self-limiting nature o f the disease process
given w i t h i n the first 2 weeks o f symptoms.
should be taken into account, symptoms improve once
the autoimmune inflammatory process is terminated,
CORTICOSTEROIDS
and the Schwann cells reverse the process to rebuild the
The role o f steroids i n GBS treatment has been widely
myelination o f the nerves. I n severe cases, the inflamma-
studied, and researchers concluded that oral corticos-
tory process can lead to axonal disruption and
teroids were not beneficial in GBS treatment and did not
permanent damage.
recommend it as the first-line therapy."'This finding is in
contrast to the standard treatment for other demyelinat-
SUPPORTIVE CARE
ing diseases for which favorable response is noted w i t h
Prevention o f life-threatening complications remains the
steroid therapy. I n 1. o f the studies, the use o f intravenous
cornerstone o f supportive care. Progressive demyehnation
corticosteroids in combination w i t h I V I g demonstrated a
o f the phrenic nerve, innervating the diaphragm, may lead
short-term improvement i n clinical symptoms when
to acute respiratory muscle paralysis. Early detection o f res-
compared to I V I g treatment a l o n e . L o n g - t e r m use o f
piratory failure and anticipation o f mechanical ventilation
corticosteroids causes numerous side effects and may
are crucial to avoid emergency intubation and cardiopul-
inhibit macrophage repair process, but short-term
monary arrest. Life-threatening episodes o f hemodynamic
treatment did not result i n serious side effects.'^
instability related to autonomic dysfunction may occur in
GBS patients (Table 4).They should be admitted to the
PAIN MANAGEMENT
hospital for close monitoring o f respiratory status, hemo-
Neuropathic pain occurs i n large number o f patients
dynamic instability, and autonomic dysfunction.
w i t h GBS and often requires recognition and treatment.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be
IMMUNOTHERAPY
tried initially, but they often do not provide adequate
Immunotherapy should be initiated as soon as possible
pain relief, as the origin o f pain is usually multifactorial.
w i t h high dose intravenous immunoglobuhn (IVIg) or
Pain in the acute phase might be nociceptive related to
plasma exchange (PE).The mechanism o f action o f I V I g
inflammation, whereas later in the course, pain may be
involves modulating the humoral response by suppressing
related to degeneration o f sensory nerve fibers.'^ Early
autoantibody production.^ I V I g also blocks the binding
recognition and treatment w i t h gabapentin or carba-
o f receptors on macrophages, suppressing the various
mazepine are suggested to be effective i n treating neuro-
inflammatory mediators. The typical dose o f I V I g is
pathic pain. Narcotic analgesics should be used w i t h
0.4g/kg per day for 5 days, started as a lower dose and
caution as they precipitate ileus in the setting o f
increased to the m a x i m u m dosage based on patient toler-
autonomic dysfunction.
ance. The goal o f PE is to remove circulating i m m u n e reactive antibodies, complements, and biological response
PROGNOSIS
modifiers.
The factors indicating poor prognosis include older age,
The treatment regimen depends on the disease severity; typically, PE is given 5 times i n 2 weeks, for a total
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infection, prolonged hospital stay, need for mechanical
ventilation and intensive care, and poor upper extremity
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647
Table 5. Complications^'
Respiratory failure, cardiac arrhythmias
Swallowing difficulties, aspiration pneumonia
Deep vein thrombosis, foot drop and joint contractures
Bladder and bowel dysfunction, paralytic ileus
weakness." G B S patients may also exhibit pain, fatigability', and functional impairments and may have permanent
neurologic impairments, such as muscle wasting, ataxia,
foot drop, and dysesthesia."^ R e c o v e r y from GBS varies;
most patients recover within 6-12 months, but some may
take longer. T h r o m b o e m b o l i c complications such as deep
vein thrombosis and pulmonary embolus may be prevented with use o f fractionated or unfractionated heparin
and compression stockings.** Early initiation o f an individualized program for muscle strengthening and physical
therapy is essential to prevent complications (Table 5).
EDUCATION AND COUNSELING
Clearly, GBS management includes applying an improved
understanding of the pathophysiology to individual
patients and the effect that it has on the vital organs and
tissues. Most patients develop secondary complications,
and tailoring o f supportive care and education should be
based on their unique needs. T h e care of a G B S patient is
challenging for the health care team and the caregivers
because some symptoms can be devastating. G B S is a life
event with a potentially long-lasting influence on physical and psychosocial well-being, transforming a healthy,
independent person into a critically ill and physically
helpless p e r s o n . ' ' T h e acute progression of motor weakness and fatigue makes a profound effect on the patient's
quahty of hfe.
Several neuromuscular disease organizations provide
resources to assist w i t h community support networks.
T h e Guillain-Barre S y n d r o m e / C h r o n i c Inflammatory
Demyelinating Polyneuropathy Foundation
(http://www.gbs-cidp.org) is an excellent place to
get support, find up-to-date information, and seek
opportunities to network.
CONCLUSION
Even though significant advances have been made
regarding the i m m u n o l o g y and pathophysiology,' o f GBS,
It is still continuing as a challenging neurological diagnosis associated with high morbiditx' and mortality. GBS
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The Journal for Nurse Practitioners - J N P
should be considered in the differential diagnosis for
patients presenting to primary care setting with lower
extremity numbness with antecedent history of upper
respiratory infection or gastroenteritis.The long-term
prognosis is dependent on early diagnosis and treatment
and knowledge o f prognostic factors can substantially
improve patient care. Biti
1. Winer JB. Guillain Barre syndrome. Mol Path. 2001;54(6l:381-385.
2. National Institute of Neurological Disorders and Stroke. Guillain-Barre
syndrome fact sheet. http://wvtfW.ninds.nih.gov/disorders/gbs/detail_gbs.htm.
Accessed July 16, 2012.
3. Khan F, Amatya B, Ng L. Use of the international classification of
functioning, disability and health to describe patient-reported disability: a
comparison of Guillain Barre syndrome with multiple sclerosis in a
community cohort. J Rehabil Med. 2010;42(B):708-714.
4. Frenzen PD. Economic cost of Guillain-Barre syndrome in the United States.
Neurology. 2008;71{l):21-27.
5. Newswanger DL, Warren CR. Guillain-Barre syndrome. Am Fam Physician.
2004;69(1):2405-2410.
6. Pithadia A, Kakadia N. Guillain-Barre syndrome. Pharmacol Rep.
2010;62(l):220-232.
7. Davids HR, Oleszek JL, Cha-Kim A. Guillain-Barre syndrome.
http://emedicine.medscape.com/article/315632. Accessed August 9, 2011.
8. Burns TM. Guillain-Barre Syndrome. Sem Neurol. 2008;28(2):1S2-167.
9. Lasky T, Terracciano GJ, Magder L, et al. The Guillain -Barre syndrome and
the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med.
1998;339(25):1797-1802.
10. Kuitwaard K, Bos-Eyssen ME, Blomkwist-Markens PH, van Doom PA.
Recurrences, vaccinations and long-term symptoms in GBS and CIDP.
J Peripher Nerv Syst. 2009;14(4):3ia-315.
11. Lehmann HC, Hartung HP Kieseier BC, Hughes RA. Guillain-Barre syndrome
after exposure to influenza virus. Lancet Infect Dis. 2010:10(9):643-65.
12. Van Doom PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and
treatment of Guillain-Barre syndrome. Lancet Neurol. 2008;7(10):939-950.
13. Winer JB. Guillain-Barre syndrome. Br Med J. 2008;337:227-231.
14. Spalice A, Parisi P Papetti L, et al. Clinical and pharmacological aspects of
inflammatory demyelinating diseases in childhood: an update. Curr
NeuropharmacoL 2010;8(2):135-148.
15. Hughes RA, Raphael JC, Swan AV, van Doom PA. Intravenous
immunoglobulin for Guillain-Barre syndrome. Cochrane Database Syst Rev.
2006;1:CD002063.
16. Bromberg MB, Carter O. Corticosteroid use in the treatment of
neuromuscular disorders: empirical and evidence-based data. Muscle Nerve.
2004;30:20-37.
17. Khan F, Pallant JF Ng L, Bhasker A. Factors associated with long-term
functional outcomes and psychological sequelae in Guillain-Barre
syndrome. J Neurol. 2010;257(12):2024-203.
18. Rudolph T, Larsen JP Farbu E. The long-term functional status in patients
with Guillain-Barre syndrome. Europ J Neurol. 2008;15(12):1332-1337.
19. Bernsen RA, de Jager AE, van der Meche FG, Suurmeijer TP How GuillainBarre patients experience their functioning after 1 year. ,4cta Neurol Scand.
2005;112(l):51-56.
Sheiiy Sebastian, DNP, R.N, NP-C, is a luirsc practitioner in
the neurosurgery department at Baylor College of Medicine in
Houston, TX, and can be reached at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business or
industry that would pose a conflict of interest.
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