CASE

A 43 year-old female presented to the emergency department complaining of fatigue. She noted two days prior, at the end of the workday, that her legs were more tired than usual. This feeling progressed over the next several days to the point where she was having difficulty walking and getting out of bed in the morning. She also noted a similar sensation in her upper extremities over the past 24 hours and tingling in all four extremities. What prompted her emergency department visit was the onset of a right sided facial droop which began about eight hours prior to arrival. She was unable to fully close her right eye and noticed drooping at the corner of her lip. She denied shortness of breath or difficulty breathing. The patient noted that she had a diarrheal illness several weeks prior to the onset of the symptoms. She denied prior medical history.  She had no previous episodes of weakness, diplopia or other visual disturbance.

The patient was febrile to 101.4 F but otherwise had normal vital signs. On physical exam, she was unable to completely close her right eye, and had some mild flattening of her right nasolabial fold. On further neurologic testing she had 3/5 strength in all muscle groups of her upper and lower extremities. Bilateral patellar and Achilles reflexes were absent.

Noncontrast CT brain was negative for intracranial mass or hemorrhage. Lab work was significant for a mild leukocytosis to 14.3, mild hypokalemia to 3.4, but was otherwise unremarkable. Negative inspiratory force (NIF) was -50 to -60 cm H2O on multiple attempts. A lumbar puncture was performed showing mildly elevated protein (63 mg/dL), but cerebrospinal fluid analysis was otherwise normal. A rapid COVID test was positive and was the likely cause of her fever.

DIAGNOSIS

Guillan-Barre syndrome (GBS), possibly Miller-Fisher variant.

DISCUSSION

GBS is a rare autoimmune phenomenon that affects about one in 100,000 people per year. It is typically preceded by a respiratory or gastrointestinal illness, most often Campylobacter, which induces an autoimmune response directed at the peripheral nervous system. The exact mechanism and contributing factors are poorly understood, however, molecular mimicry seems to play a role in some cases. Although GBS is thought of as a demyelinating disease there are actually two discrete phenotypes: demyelination polyneuropathy (more common in the United States) and axonal injury neuropathy. In the former, autoantibodies are directed at the myelin sheath and Schwann cells, whereas they target the axonal cell membrane in the latter. This distinction is inconsequential in the emergency setting as both present with similar patterns of ascending weakness and are managed the same way. In the Miller-Fisher variant of GBS, autoantibodies attack a specific ganglioside that is rich in extraocular motor neurons, commonly resulting in ocular paralysis, but can affect other cranial nerves as well. [1]

The natural history of GBS sees the acute onset of ascending paralysis starting 1-2 weeks after the infectious insult with symptoms peaking in 2-4 weeks. During this progressive phase 20-30% of patients develop respiratory failure requiring intubation and mechanical ventilation. The ensuing recovery phase can be highly variable. Patients may experience only minor symptoms and recover spontaneously.  Severe cases may result in quadriplegia, require long-term mechanical ventilation and may not show signs of improvement for months or more. While essentially all patients see improvement in their symptoms, full recovery is not guaranteed and permanent deficits are a possibility. [1]

The diagnosis of GBS is clinical requiring ascending weakness and arreflexia in the affected limbs. A history that fits the expected disease course is helpful and other symptoms such as sensory deficits, pain, cranial nerve involvement and bulbar symptoms, and autonomic dysfunction (e.g. cardiac arrhythmia, sweating, blood pressure instability) are consistent with the diagnosis. CSF analysis can be a useful adjunct with the classic finding of cytoalbuminologic dissociation -- elevated protein with a normal cell count. Unfortunately, protein levels will eventually normalize, and a normal CSF analysis of a late-presenting patient cannot be used to exclude the diagnosis. [1]

As previously mentioned, about one-third of GBS patients will develop respiratory failure requiring intubation and mechanical ventilation. [2] Useful adjuncts to assess respiratory status are negative inspiration force (NIF) and forced vital capacity (FVC). The former is a measurement of diaphragmatic strength but the latter may be more useful, as it encompasses both inspiration and expiratory effort. NIF is performed by forcefully inhaling to maximum lung capacity. FVC is measured by inhaling deeply, then forcefully expelling as much air as possible from their lungs. [3] A NIF <30 cm water or FVC <20 mL/kg are concerning for impending respiratory failure, however, the decision to intubate should not be based on these values alone. Clinical assessment is more important including work of breathing, respiratory rate, oxygenation and the changes in these variables over time. [4] If intubation is indicated succinylcholine should be avoided due to the risk of hyperkalemia in neuromuscular disease.

Other than close monitoring of respiratory status patients will need cardiorespiratory monitoring for possible hemodynamic instability secondary to autonomic dysfunction. In rare cases severe bradycardia may occur requiring pacemaker placement. [2] 

The mainstay of treatment is intravenous immunoglobulin (IVIG) which has mostly supplanted plasma exchange.  IVIG is convenient to give, widely available and has few side effects. IVIG is most effective when started within two weeks of symptom onset. [1] 

Disposition is institution-dependent, but patients will likely need intermediate level of care for close monitoring of their respiratory status with frequent NIF/FVC measurements. Indications for intensive care unit include impending respiratory failure, intubation, significant autonomic or bulbar dysfunction, rapidly progressing weakness and plasmapheresis. [5]

CASE RESOLUTION

The patient was admitted to an intermediate level of care for close monitoring of her respiratory status. She completed a 5 day course of IVIG, during which her symptoms improved. She maintained normal NIFs during her hospitalization. Her deficits had not completely resolved at the time of her discharge, and she was discharged home with physical therapy following.

TAKE-AWAYS

• GBS is a clinical diagnosis, requiring a history of ascending weakness and lower extremity arreflexia, typically preceded by a respiratory or gastrointestinal illness.

• CSF may show cytoalbuminologic dissociation but a normal protein does not exclude the diagnosis.

• NIF <30 cm water or FVC <20 mL/kg are concerning signs of respiratory failure but the decision to intubate should be based on clinical judgement.

AUTHOR: Daniel Coleman is a fourth-year emergency medicine resident at Brown University/Rhode Island Hospital.

FACULTY REVIEWER: Kristina McAteer is an Assistant Professor of Emergency Medicine and Clinician Educator at Brown/Rhode Island Hospital.

References

1. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. 2016 Aug 13;388(10045):717-27.

2. Steinburg J. What Emergency Physicians Should Know About Guillain-Barré Syndrome. ACEP Now. 2016 Jan 20. Accessed 2020 Jan 27. https://www.acepnow.com/article/emergency-physicians-know-guillain-barre-syndrome/

3. Emory ALS Center. Resource Guide: Section 4 - Breathing. Accessed 2020 Jan 27. https://med.emory.edu/departments/neurology/programs_centers/emory_als_center/_documents/breathing.pdf

4. Farkas J. Five pearls for the dyspneic patient with Guillain-Barre Syndrome or Myasthenia Gravis. EM Crit. 2015 Feb 22. Accessed 2020 Jan 27. https://emcrit.org/pulmcrit/five-pearls-for-the-dyspneic-patient-with-guillain-barre-syndrome-or-myasthenia-gravis/

5. Leonhard SE, Mandarakas MR, Gondim FAA et al. Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol. 2019 Nov;15(11):671-683.