Guillain-Barré Syndrome Case File

Guillain-Barré Syndrome Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 39

A 25-year-old woman with no previous medical issues is brought into the emergency room (ER) after tripping during a volleyball match. Her teammate notes that she had been stumbling and was starting to have more difficulty with her serve. On arrival, she can no longer raise her legs and labors to adjust herself in bed. She has also begun to complain of shortness of breath. She denies fever but states that 3 weeks ago the entire team suffered from abdominal cramps and diarrhea after a championship cookout. On examination, she appears weak and slightly dyspneic. Her temperature is 36.6°C (98°F); heart rate is 50 beats/min; respiration rate is 26 breaths/min; and blood pressure is 90/60 mm Hg. Her pupils are sluggish, and she constantly clears her throat. She can only keep her arms up against gravity for 10 seconds, and her hands are limp. She has slight movement of her legs, with decreased sensation of pain and fine touch to her knees. Her reflexes are absent. She has no skin lesions. Her heart and lung examinations are unremarkable except for bradycardia and poor inspiratory effort. The abdominal examination reveals normoactive bowel sounds and no masses. Her complete blood count (CBC) is unremarkable. The pregnancy test is negative. Magnetic resonance imaging (MRI) scans of the brain and spine are normal.

▶ What is the most likely diagnosis?

▶ What is the next diagnostic step?

▶ What is the next step in therapy?

ANSWERS TO CASE 39:

Guillain-Barré Syndrome                                                   

Summary: A 25-year-old previously healthy woman presents to the ER with rapid progression of ascending weakness with diaphragmatic involvement. She has a

history of gastroenteritis 3 weeks before presentation. She is bradycardic, tachypneic, and hypotensive. The neurologic examination is significant for areflexia, paralysis of her legs with sensory deficits, severe weakness of her arms, and some difficulty swallowing and breathing.

• Most likely diagnosis: Guillain-Barré syndrome, specifically acute inflammatory demyelinating polyneuropathy (AIDP).
• Next diagnostic step: Lumbar puncture for elevated protein level with few cells (cytoalbuminologic dissociation).
• Next step in therapy: Forced vital capacity (FVC) and negative inspiratory force (NIF) with consideration of intubation and mechanical ventilation for FVC less than 20 mL/kg, or NIF worse than –30 cm H2O.

ANALYSIS

Objectives

1. Know a diagnostic approach to Guillain-Barré syndrome, including historical clues and examination findings, and understand the differential diagnosis.
2. Understand that addressing respiratory failure should be the first priority in treating acute weakness caused by Guillain-Barré syndrome.
3. Be familiar with a rational workup for Guillain-Barré syndrome and know the subtypes, including the Miller-Fisher variant.

Considerations

This 25-year-old woman developed acute symmetric ascending paralysis with progressive involvement of diaphragmatic muscles. Her most immediate problem is impending respiratory failure. The first priority should be to determine the progression of respiratory insufficiency, usually by serially measuring FVC. The NIF should also be followed. Oxygen desaturation occurs much too late to be a safe indicator. An FVC less than 15 to 20 mL/kg or NIF worse than –30 cm H2O usually signals imminent need for intubation and mechanical ventilation. After determining the need for intubation, the next priority is to determine the etiology of the weakness.

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis in the United States, occurring in 1 to 3 out of every 100,000 people with a bimodal distribution affecting patients of 15 to 35 years and 50 to 75 years. This patient has the classic history of a bacterial or viral gastrointestinal illness 2 to 4 weeks prior to onset of paresthesia and weakness. She had been exposed to poorly cooked meat, which predisposes her to Campylobacter jejuni. Forty percent of Guillain-Barré

patients have positive C. jejuni serum antibodies and/or stool cultures. Areflexia is a hallmark examination finding, particularly in conjunction with proximal lower extremity weakness with distal sensory changes and ascending progression. Diaphragmatic and cranial nerve muscles can be affected as well, with up to one-third of patients requiring intubation, as well as autonomic involvement causing bradycardia and hypotension.

APPROACH TO:

Acute Weakness                                                      

DEFINITIONS

ACUTE ASCENDING WEAKNESS: Ascends from legs to arms and cranial nerves over hours to days.

INFLAMMATORY: Autoimmune humoral and cell-mediated response to recent infection. This response is capable of molecular mimicry to stimulate production of antiganglioside antibodies against surface molecules of peripheral nerves.

DEMYELINATING: Damage to myelin surrounding the peripheral nerves, spinal roots, and cranial nerves resulting in clinical weakness and numbness, and electromyographic evidence of profoundly delayed or absent nerve conduction velocities.

POLYNEUROPATHY: Symmetric damage to peripheral nerves in multiple extremities.

FLACCID: Lower motor neuron weakness with hypo- or areflexia, hypotonia, and, in the case of chronic disease, muscle atrophy.

CLINICAL APPROACH

Acute weakness can be associated with conditions affecting all levels of the nervous system. However, the pattern of weakness, presence of other signs (sensory loss, incoordination, altered mental status), and degree of hypo- or hyperreflexia help to distinguish the anatomic site of disease.

Disorders of the brain that cause acute weakness include acute stroke, space-occupying lesion, or an inflammatory or infectious cause. Often, these conditions affect multiple pathways, resulting not only in motor weakness but also in sensory changes, speech changes, and altered mental status. In this case, the patient presented with a rapidly ascending, bilateral, and respiratory weakness, in the absence of speech changes. Her reflexes were absent, and her level of consciousness was intact. Therefore, it is unlikely that her condition was caused by a primary disease of the brain, as central nervous system (CNS) disease often results in unilateral involvement in association with increased reflexes. Further, those conditions that affect both sides of the brain and cause bilateral weakness are often diffuse and affect speech and mentation. The exception to this is spinal cord disease, which can result in symmetric weakness and sensory loss that can ascend from the legs, depending on the condition. Therefore, it is often worthwhile to image the spinal cord in such clinical presentations. In this case, the patient's spinal cord was normal and the clinical presentation was most consistent with a condition of the peripheral nervous system (PNS).

The PNS is made up of the nerve root, peripheral nerve, nerve-muscle junction, and muscle. Myopathies of various etiologies often present with a subacute or chronic course associated with proximal muscle weakness, which typically does not ascend. Although muscle diseases such as inflammatory myopathies, muscular dystrophies, and metabolic myopathies can be associated with respiratory impairment, the sensory and autonomic systems are not affected.

Nerve-muscle junctional disorders such as myasthenia gravis can present with acute and subacute motor weakness that fatigues with repetitive activity. However, the examination in this case did not reveal impairment or fatigue due to disorders of the neuromuscular junction.

Guillain-Barré syndrome can be associated with C. jejuni as well as other bacterial etiologies, including Haemophilus influenzae, Mycoplasma pneumoniae, and Borrelia burgdorferi, and viral etiologies such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most recently, there have been reported cases of cases associated with the Zika virus, but further research to confirm this possibility is still ongoing. In addition, postvaccination disease, especially influenza, has been reported, as well as rare cases associated with systemic lupus erythematosus, sarcoidosis, lymphoma, postpregnancy, and certain medications.

There are five major subtypes of Guillain-Barré syndrome; the most common in the western hemisphere is AIDP. The Miller-Fisher variant presents with the textbook triad of areflexia, ataxia (out of proportion to sensory deficits), and ophthalmoplegia, as well as predominant cranial nerve weakness rather than extremity weakness, and positive anti-GQ1b (ganglioside) antibodies. Acute motor-axonal neuropathy (AMAN) is purely motor and affects mostly children, with greater than 70% being seropositive for C. jejuni. It usually carries a better prognosis for recovery. Acute motor-sensory axonal neuropathy (AMSAN) is more common in adults and generally causes significant muscle atrophy with poor prognosis for recovery. Acute panautonomic neuropathy is the rarest subtype and is associated with high mortality from cardiovascular involvement and dysrhythmias.

The differential diagnosis for acute flaccid paralysis with gastrointestinal symptoms includes two very important etiologies that carry high morbidity but, if identified and treated quickly, can be reversed: botulism and tick paralysis. Botulism is caused by the Clostridium botulinum neurotoxin and is frequently foodborne but can also present as a result of intravenous drug use, surgery, and wound complications. The difference is that patients with botulism present with a descending paralysis, beginning with the Dozen Ds of cranial nerve progression.

• Dry mouth
• Double vision
• Dilated pupil
• Droopy eyelids
• Drooping face
• Diminished gag reflex
• Dysphagia
• Dysarthria
• Dysphonia
• Difficulty lifting head
• Descending paralysis
• Diaphragmatic paralysis

Rapid administration of botulism antitoxin halts worsening, although mechanical ventilation can still be required. Tick paralysis produces a rapidly ascending paralysis with areflexia, ataxia, and respiratory insufficiency much like Guillain-Barré syndrome, particularly in children with a history of outdoor exposure. Removal of the discovered female tick can be curative by elimination of the source of the neurotoxin.

CLINICAL PRESENTATION

The mean interval from onset of Guillain-Barré syndrome to the most severe degree of impairment is 12 days, with 98% of patients reaching the endpoint of clinical worsening (nadir) by 4 weeks. The mean time to improvement starts at 28 days, and clinical recovery usually occurs by 200 days. Although 85% of patients recover completely, up to 15% have permanent deficits. Three to eight percent of patients die in spite of intensive care management. A major cause of mortality in elderly victims is arrhythmia.

The history should identify corroborating symptomatology and triggers as discussed above and should rule out other causes of acute flaccid paralysis. The physical examination should focus on the vital signs, reflexes, and extent of weakness in the extremities, diaphragm, and cranial nerves. Fever and mental status changes are unusual and signal hypoxic respiratory failure or a different etiology. An important diagnostic test is the lumbar puncture, which shows rising protein levels up to 400 mg/L with no associated increase in cell count (cytoalbuminologic dissociation), although protein elevation may not be seen until 1 to 2 weeks after onset, and in 10% of cases it remains normal. Antibodies and stool culture for C. jejuni are frequently checked. Other helpful tests include sedimentation rate, antiganglioside antibodies, anti-GQ1b antibodies for Miller-Fisher presentations, and a pregnancy test. The presence of anti-GM1 antibodies is typically associated with a poor prognosis.

Nerve conduction studies show early changes indicative of nerve root demyelination. MRI of the brain and spine can show anterior nerve root enhancement, which is more specific for Guillain-Barré syndrome but should be obtained in all cases to rule out other secondary causes such as malignancy, vasculitides, viral infections, or spinal cord pathology. Measurement of respiratory strength (FVC) is crucial for cases with respiratory involvement. An electrocardiograph (ECG) should be performed to screen for atrioventricular (AV) block, ST-segment changes, and arrhythmias.

The patient should be admitted for further monitoring and treatment. If the etiology is still unclear and the patient continues to deteriorate, consultation with a neurologist is indicated.

TREATMENT

Intubation and mechanical ventilation should be considered for FVC less than 15 mL/kg or NIF worse than –30 cm H2O, with intensive care monitoring for the presence of arrhythmias and blood pressure instability. Because of the immune-mediated pathogenesis of the disease, the only proven therapies to date are IV immunoglobulin (IVIg) and plasma exchange, both of which can hasten recovery by 50% if initiated early in the course of the disease. There are no data to support the use of steroids. Complications of immobility, hospitalization, and respiratory insufficiency should be avoided by implementing prophylactic measures for deep venous thrombosis, decubitus ulcers, gastritis, and aspiration. Recurrence is rare but can occur in up to 5% of cases.

CASE CORRELATION

• See also Case 38 (Chronic Inflammatory Demyelinating Polyneuropathy) and Case 40 (Dermatomyositis)

COMPREHENSION QUESTIONS

Match the following etiologies (A-F) to the clinical situation 39.1 to 39.5:

A. Acute inflammatory demyelinating polyneuropathy

B. Miller-Fisher syndrome

C. Myasthenia gravis

D. Inflammatory myopathy

E. Tick paralysis

F. Acute stroke

39.1 A 25-year-old man presents with difficulty walking and foot numbness 2 weeks after the resolution of fever and bloody diarrhea.

39.2 An 18-year-old woman returns from a camping trip complaining of blurry vision, facial weakness, and difficulty swallowing. She subsequently develops arm and leg weakness.

39.3 A 65-year-old man with hypertension and diabetes presents with acute right face, arm, leg weakness, slurred speech, and right-sided hyperreflexia.

39.4 A 34-year-old woman presents with muscle weakness after climbing stairs or blow-drying her hair that improves with rest.

39.5 A 28-year-old man presents with ataxia, double vision, and absent deep tendon reflexes 3 weeks following the onset of cough and fever.

ANSWERS

39.1 A. Acute inflammatory demyelinating polyneuropathy is the most common presentation of Guillain-Barré syndrome, with up to 60% of patients seropositive for C. jejuni, which is mostly found in poorly cooked meats.

39.2 E. Tick paralysis presents with ascending paralysis and resolves with removal of the tick. This patient developed her symptoms immediately after a camping trip, which makes tick bite paralysis a strong suspicion.

39.3 F. This older patient has multiple risk factors of cardiovascular disease and presents with unilateral face, arm, and leg weakness and dysarthria, which are consistent with an acute cerebrovascular event.

39.4 C. Myasthenia gravis is an acquired neuromuscular junction disorder caused by antibody-mediated impairment of the skeletal muscle acetylcholine receptor. Fatigability and improvement with rest are hallmarks of the disease.

39.5 B. Miller-Fisher syndrome typically presents with the classic triad of ataxia, ophthalmoplegia, and areflexia and is a common variant of Guillain-Barré syndrome. There is often an antecedent viral infection or Campylobacter infection.

    CLINICAL PEARLS    

▶ The majority of Guillain-Barré cases are associated with a history of preceding C. jejuni or other flu-like or gastrointestinal syndromes. ▶ Most Guillain-Barré patients experience proximal lower extremity weakness with ascending paralysis within hours to days. ▶ One should be wary that the examination can worsen rapidly from one visit to the next, with the possibility of respiratory failure. ▶ Significant autonomic instability can accompany Guillain-Barré symptoms and require intensive care monitoring. ▶ IV immunoglobulin and plasma exchange are the two therapeutic options that have been shown to improve recovery.

REFERENCES

Hughes RA, Cornblath DR. Guillain-Barré syndrome. Lancet. 2005;366(9497):1653-1666. van den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, van Doorn PA. Guillain-Barre syndrome: pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol. 2014;10:469-482. 

Winer JB, Jacob S. Guillain-Barre syndrome. BMJ Best Practice April 2015. http://bestpractice.bmj.com/best-practice/monograph/176.html. Accessed March 3, 2016. 

World Health Organization. Identification and management of Guillain-Barré syndrome in the context of Zika virus. http://apps.who.int/iris/bitstream/10665/204474/1/WHO_ZIKV_MOC_16.4_eng.pdf?ua=1. Accessed September 3, 2016. 

Zautner AE, Johann C, Strubel A, et al. Seroprevalence of campylobacteriosis and relevant post-infectious sequelae. Eur J Clin Microbiol Infect Dis. 2014;33(6)1019-1027.

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