A 25-year-old female is brought into the arms, and some difficulty swallowing and

emergency room (ER) after tripping during a breathing. The pregnancy test is negative.
volleyball match. Her teammate notes that ◆ Most likely diagnosis: Guillain-Barré
she had been stumbling and was starting to syndrome or acute inflammatory
have more difficulty with her serve. On demyelinating polyneuropathy (AIDP)
arrival, she can no longer raise her legs and ◆ Next diagnostic step: Lumbar puncture
labors to adjust herself in bed. She has also for elevated protein level with few cells
begun to complain of shortness of breath. (albuminocytologic dissociation)
She denies fever but states that 3 weeks ago ◆ Next step in therapy: Forced vital
the entire team suffered from abdominal capacity with prophylactic intubation and
cramps and diarrhea after a championship mechanical ventilation for forced vital
cookout. The patient denies previous health capacity (FVC) less than 15–20 mL/kg
problems. On examination, she appears
weak and slightly dyspneic. Her temperature ANALYSIS
is 36.6°C (98°F); heart rate, 50 beats/min; Objectives
respiration rate, 26 breaths/min; and blood 1. Know a diagnostic approach to Guillain-
pressure, 90/60 mmHg. Her pupils are Barre syndrome including historical clues and
sluggish, and she constantly clears her examination findings, and understand the
throat. She can only keep her arms up differential diagnosis.
against gravity for 10 seconds, and her hands 2. Understand that addressing respiratory
are limp. She has slight movement of her failure should be the first priority in treating
legs with decreased sensation of pain and acute weakness caused by Guillain-Barré
fine touch to her knees. Her reflexes are syndrome.
absent. She has no skin lesions. Her heart 3. Be familiar with a rational workup for
and lung examinations are unremarkable Guillain-Barré syndrome, and know the
except for bradycardia and poor inspiratory subtypes including the Miller Fisher variant.
effort. The abdominal examination reveals Considerations
normoactive bowel sounds and no masses. This 25-year-old woman developed acute
Her complete blood count is unremarkable. symmetric ascending paralysis with
The pregnancy test is negative. MRI of the progressive involvement of diaphragmatic
brain and spine are normal. muscles. Her most immediate problem is
◆ What is the most likely diagnosis? impending respiratory failure. The first
◆ What is the next diagnostic step? priority should be to determine the
◆ What is the next step in therapy? progression of respiratory insufficiency,
usually by serially measuring FVC. The
ANSWERS TO CASE 39: Guillain-Barré negative inspiratory force should also be
Syndrome followed. Oxygen desaturation occurs much
Summary: A 25-year-old healthy female too late to be a safe indicator. An FVC less
presents to the ER with rapid progression of than 15–20 mL/kg or maximum inspiratory
ascending weakness with diaphragmatic pressure less than 30 cm H2O usually
involvement. She has a history of signals imminent need for intubation and
gastroenteritis 5 weeks before presentation. mechanical ventilation. After determining the
She is bradycardic, tachypneic, and need for intubation, the next priority is to
hypotensive. The neurologic examination is determine the etiology of the weakness.
significant for areflexia, paralysis of her legs Guillain-Barré syndrome is the most
with sensory deficits, severe weakness of her common cause of acute flaccid paralysis
in the United States, occurring in 1–3 out of Acute motor weakness can be
every 100,000 people with a bimodal associated with conditions affecting all levels
distribution affecting patients 15–35 years of of the nervous system. However, the pattern
age and 50–75 years of age. This patient has of weakness, presence of other signs
the classic history of a bacterial or viral (sensory loss, incoordination, altered mental
gastrointestinal illness 2–4 weeks prior to status) and degree of hypo- or hyperreflexia
onset of paresthesia and weakness. She had helps to distinguish the anatomic site of
been exposed to poorly cooked meat, which disease.
predisposes her to Campylobacter jejuni. Disorders of the brain that cause acute
Forty percent of Guillain-Barré patients have weakness include acute stroke, space
positive C. jejuni serum antibodies and/or occupying lesion, or an inflammatory or
stool cultures. Areflexia is a hallmark infectious cause. Often these conditions
examination finding, particularly in affect multiple pathways resulting in not only
conjunction with proximal lower extremity motor weakness, but sensory changes,
weakness with distal sensory changes and speech changes, and altered mental status.
ascending progression. In this case, the patient presented with a
Diaphragmatic and cranial nerve muscles can rapidly ascending, bilateral weakness and
be affected as well, with up to one-third of respiratory weakness, in the absence of
patients requiring intubation, as well as speech changes. Her reflexes were absent,
autonomic involvement causing the and her level of consciousness is intact.
bradycardia and hypotension. Therefore, it is unlikely that her condition is
caused by disease of the brain. Further CNS
APPROACH TO ACUTE WEAKNESS disease often results in unilateral involvement
Definitions in association with increased reflexes.
Acute weakness: Ascends from legs to arms Further, those conditions that affect both
and cranial nerves over hours to days. sides of the brain and cause bilateral
Inflammatory: Autoimmune humoral and weakness, are often diffuse and affect
cell-mediated response to recent infection speech and mentation. The exception to this
capable of molecular mimicry to stimulate is spinal cord disease, which can result in
production of antiganglioside antibodies symmetric weakness and sensory loss that
against surface molecules of peripheral can ascend from the legs, depending on the
nerves. condition. Therefore, it is often worthwhile to
Demyelinating: Immune-mediated damage image the spinal cord in such clinical
to myelin surrounding the peripheral nerves, presentations. In this case, the patient’s
spinal roots, and cranial nerves resulting in spinal cord was normal. Therefore, the
clinical weakness and numbness, and presentation is most consistent with a
electromyographic evidence of profoundly condition of the peripheral nervous system.
delayed or absent nerve conduction The peripheral nervous system (PNS)
velocities. is made up of the nerve root, peripheral
Polyneuropathy: Symmetric damage to nerve, nerve-muscle junction, and muscle.
peripheral nerves in multiple extremities. Myopathies of various etiologies often
Flaccid: Lower motor neuron weakness with present with a subacute or chronic course
hypo- or areflexia, hypotonia, and, in the case associated with proximal muscle weakness,
of chronic disease, muscle atrophy. which typically does not ascend. Although
muscle diseases such as inflammatory
Clinical Approach myopathies, muscular dystrophies, and
metabolic myopathies can be associated with recovery. Acute panautonomic neuropathy is
respiratory impairment, the sensory and the rarest subtype with mortality from
autonomic systems are not affected. cardiovascular involvement and
Nerve-muscle junctional disorders dysrhythmias. The differential diagnosis for
such as myasthenia gravis can present with acute flaccid paralysis with gastrointestinal
acute and subacute motor weakness that symptoms includes two very important
fatigues with repetitive activity. etiologies that carry high morbidity but, if
However, the examination in this case did not identified and treated quickly, can be
reveal impairment or fatigue of reversed: botulism and tick paralysis.
the neuromuscular junction. Botulism is caused by the Clostridium
In this case, the acute onset of a botulinum neurotoxin, the most lethal toxin
flaccid ascending, symmetric weakness and known to man, and is frequentlyfood-borne
presence of autonomic dysfunction is most but can also present with intravenous drug
consistent with an acute polyneuropathy. The use, surgery, and wounds. The difference is
etiologies of acute or subacute that patients present with a descending
polyneuropathy is not extensive. In an paralysis, beginning with the Dozen Ds of
otherwise healthy young girl, the presentation cranial nerve progression—dry mouth, double
is most consistent with acute inflammatory vision, pupil dilation, droopy eyelids, facial
demyelinating polyneuropathy (AIDP) or droop, diminished gag reflex, dysphagia,
Guillain-Barré syndrome. dysarthria, dysphonia, difficulty lifting head,
Guillain-Barré syndrome can be associated descending paralysis, and diaphragmatic
with C. jejuni as well as other bacterial paralysis. Rapid administration of botulism
etiologies including Haemophilus influenzae, antitoxin halts worsening, although
Mycoplasma pneumoniae, and Borrelia mechanical ventilation can still be required.
burgdorferi, and viral etiologies such as HIV, Tick paralysis produces a rapidly ascending
Cytomegalovirus (CMV), and Epstein-Barr paralysis with areflexia, ataxia, and
virus (EBV). Postvaccination disease, respiratory insufficiency much like Guillain-
especially influenza, has been reported, as Barré syndrome, particularly in children with a
well as rare cases associated with systemic history of outdoor exposure. Removal of the
lupus erythematosus, sarcoidosis, lymphoma, discovered female tick can be curative by
postpregnancy, and certain medications. elimination of the source of the neurotoxin.
There are five major subtypes of Guillain-
Barré syndrome, the most common by far Clinical Presentation
being AIDP. The Miller-Fisher variant The mean interval from onset of
presents with the textbook triad of areflexia, Guillain-Barré syndrome to the most severe
ataxia (out of proportion to sensory deficits), degree of impairment is 12 days, with 98% of
and ophthalmoplegia, predominant cranial patients reaching the end point of clinical
nerve weakness rather than extremities, and worsening (nadir) by 4 weeks. The mean time
positive anti-GQ1b (ganglioside) antibodies. to improvement starts at 28 days, and clinical
Acute motoraxonal neuropathy (AMAN) is recovery usually occurs by 200 days. Eighty-
purely motor and affects mostly children, with five percent of patients recover completely,
greater than 70% being seropositive for C. although up to 15% have permanent deficits.
jejuni. It usually carries a better prognosis for Three to eight percent of patients die in spite
recovery. Acute motor-sensory axonal of intensive care management. A major
neuropathy (AMSAN) affects more adults, cause of mortality in elderly victims is
with significant muscle atrophy and poor arrhythmias.
 The history should be meticulous to arrhythmias and blood pressure
identify corroborating symptomatology and instability. Because of the immune-mediated
triggers as discussed above, and to rule out pathogenesis of the disease, the only proven
other causes of acute flaccid paralysis. The therapies are IV immune globulin therapy (5
physical examination should focus on the days) and plasma exchange (10 days), both
vital signs, reflexes, and extent of weakness of which can hasten recovery by 50% if
in the extremities, diaphragm, and cranial initiated early in the course of the disease.
nerves. Fever and mental status changes are There is no data to support the use of
unusual, and signal hypoxic respiratory steroids. Complications of immobility,
failure or a different etiology. The principal hospitalization, and respiratory insufficiency
laboratory test is the lumbar puncture should be avoided by implementing
showing rising protein levels up to 400 mg/L prophylactic measures for deep venous
with no associated increase in cell count thrombosis, decubitus ulcers, gastritis, and
(albuminocytologic dissociation), although aspiration. Recurrence is rare but can occur
protein elevation may not be seen until 1–2 in up to 5% of cases.
weeks after onset, and 10% remain normal.
Antibodies and stool culture for C. jejuni are CLINICAL PEARLS
frequently checked. Other helpful tests ❖ The majority of Guillain-Barré cases are
include sedimentation rate, antiganglioside associated with a history of preceding C.
antibodies, anti-GQ1b antibodies for Miller jejuni or other flu-like or gastrointestinal
Fisher presentations, and pregnancy test. syndrome.
Presence of anti-GM1 antibodies signals a ❖ Most Guillain-Barré patients experience
poorer prognosis. Nerve conduction studies proximal lower extremity weakness with
show early changes indicative of nerve root ascending paralysis within hours to days.
demyelination. MRI of the brain and spine ❖ One should be wary that the examination
can show anterior nerve root enhancement, can worsen rapidly from one visit to the next
which is more specific for Guillain-Barré with the possibility of respiratory failure.
syndrome, but should be obtained for difficult
❖ Significant autonomic instability can
cases to rule out secondary causes, such as
accompany Guillain-Barré symptoms and
malignancy, vasculitic, or viral infection, and
require intensive care monitoring.
spinal cord pathology. Measurement of
❖ IV immunoglobulin and plasma exchange
respiratory strength (FVC) is crucial for cases
with respiratory involvement as above. are the two therapeutic options that have
Electrocardiograph (ECG) should be been shown to improve recovery.
performed to screen for atrioventricular block,
ST segment changes, and arrhythmias. Reference:
The patient should be admitted for Toy, C.E., Simpson, E., Pleitez, M., David,
further monitoring and treatment. If the R., & Tintner, R. (2008). Case 39. In Case
etiology is still unclear and the patient Files Neurology (pp. 329-335). doi:
continues to deteriorate, consultation 10.1036/0071482873
with a neurologist is indicated.

Treatment
Intubation and mechanical ventilation
should be considered for FVC less than 15
mL/kg with intensive care monitoring for