Patient Presentation
An 18-year-old female came to clinic with bilateral leg soreness that she felt was not increasing over the past 4 days. She was actually improving at presentation. It worsened with walking up stairs, or when moving from a seated or squatted position to an upright position. She denied pain in other muscle groups or in the actual lower extremity joints. She also denied any paresthesia, difficulty with walking, urinating or defecating, or changes in urine color. She denied any fever, chills, nausea, or difficulty breathing, speaking or swallowing. She had upper respiratory symptoms the week before but had greatly improved. The family was concerned because her past medical history was positive for classic Guillian-Barré syndrome (GBS) when she was 9 years old that was not associated with influenza vaccine and no specific infectious disease was identified by culture at the time. She had slowly improved over 5 months and had no residual symptoms since that time. With more questioning, she noted that she had a big weight lifting workout for gym class the same day as she helped a friend move some boxes on the day before the pain began. “I guess that could be the cause. I didn’t really think about that,” she noted. The family history was negative for neurological disease. The review of systems was negative.

The pertinent physical exam showed a healthy female with normal growth parameters and vital signs. HEENT showed some residual minor rhinorrhea. Her neurological examination was normal including normal sensation and brisk lower and upper extremity reflexes. She had normal strength and tone. She endorsed some minor pain with palpation of the bilateral quadriceps muscles.

The diagnosis of muscle overuse was made. “You have a normal neurological examination and all the other things I would be worried about are negative. No problems with sensing things, walking, breathing, etc. I think you overused your muscles and are sore but getting better,” the pediatrician noted. He went on, “Its influenza season and I know that you and your parents haven’t given you a vaccine usually, but I just want to make sure you don’t have some other reason that would make you high risk now and then you should really get it.” After reviewing high risk individuals, he remarked, “We don’t give the vaccine for people with Guillian-Barré syndrome if they got it within 6 weeks of influenza vaccination. Your Guillian-Barre was not within 6 weeks, so you can get the vaccine. Especially if you become high risk then it is recommended to get it. One thing is if you want to go to medical school as you have told me, that would put you at high risk for flu.”

Discussion
Guillian-Barré syndrome (GBS) is an acquired, acute, inflammatory, demyelinating polyneuropathy. It is the most common cause of acute and subacute flaccid paralysis in children. GBS causes about 0.4-1.3 cases per 100,000 persons/year in children. It can occur in any age group and the incidence increases among all age groups until a peak in the 50s. Both genders are affected and there may be a slight increase in males.

GBS usually occurs 2-4 weeks after a prodromal gastroenteritis or respiratory illness. GBS causes autoantibody production against Schwann cells of the neuron and the axon itself. There is an increase in anti-ganglioside antibodies which can be specifically identified in about 50% of children.

Classically GBS is a symmetric, progressive ascending muscle weakness and/or paralysis usually first occurring in the legs and then ascending to the upper extremities usually over days to weeks. Areflexia or diminished deep tendon reflexes are early signs (usually first week) if the patient comes to attention. Reflexes can be preserved in some patients though. Sensory changes including pain or paraesthesia can be a first sign in up to 50% of children. The pain can be poorly localized or vocalized because of the children’s age and development. Patients can appear to be ataxic but with further examination this is due to muscle weakness and sensory changes, not actual ataxia. Patients are afebrile.

The nadir when symptoms are the worst is usually around 2 weeks after symptoms begin and most patients begin improving after that. Most have significant improvement by 4 months and most have full recovery. Persistent symptoms can occur with fatigue being the most common, but also paresthesia and pain. Some still have problems including fatigue and sensory issues long term. A review of GBS can be found here.

Learning Point
Recurrences of GBS where patients have 2 or more attacks with an acute inflammatory demyelinating neuropathy are rare. The recurrence rate is quoted as 1-6% with asymptomatic periods ranging from a few months to years (2 months – 37 years depending on the study).

Some studies have demonstrated no incidence of recurrent GBS after seasonal influenza vaccination, and that at the minimum the risk is very small. Therefore GBS has a precaution against seasonal influenza vaccine. The Centers for Disease Control state that “A history of Guillain-Barre Syndrome (GBS) within 6 weeks following a previous dose of any type of influenza vaccine is considered a precaution to vaccination…. Persons who are not at higher risk for severe influenza complications…and who are known to have experienced GBS within 6 weeks of a previous influenza vaccination generally should not be vaccinated. As an alternative to vaccination, physicians might consider using influenza antiviral chemoprophylaxis for these persons…. However, the benefits of influenza vaccination might outweigh the risks for certain persons who have a history of GBS and who also are at higher risk for severe complications from influenza.”

Questions for Further Discussion
1. What groups or individuals are considered high risk for influenza?
2. What causes ataxia? Click here for a differential diagnosis.
3. What causes muscle weakness with and without hypotonia? Click here for a differential diagnosis.

Related Cases

Disease: Guillain-Barre Syndrome

Symptom/Presentation: Pain

Specialty: Neurology / Neurosurgery

Age: Teenager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Guillian-Barre Syndrome

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To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

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Koul R, Chacko A, Ahmed R, Varghese T, Javed H, Al-Lamki Z. Ten-year prospective study (clinical spectrum) of childhood Guillain-Barre syndrome in the Arabian peninsula: comparison of outcome in patients in the pre- and post-intravenous immunoglobulin eras. J Child Neurol. 2003 Nov;18(11):767-71.

Stowe J, Andrews N, Wise L, Miller E. Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenza like illness using the United Kingdom General Practice Research Database. Am J Epidemiol. 2009 Feb 1;169(3):382-8.

Kuitwaard K, Bos-Eyssen ME, Blomkwist-Markens PH, van Doorn PA. Recurrences, vaccinations and long-term symptoms in GBS and CIDP. J Peripher Nerv Syst. 2009 Dec;14(4):310-5.

Roodbol J, de Wit MC, Aarsen FK, Catsman-Berrevoets CE, Jacobs BC. Long-term outcome of Guillain-Barre syndrome in children. J Peripher Nerv Syst. 2014 Jun;19(2):121-6.

Gunatilake SS, Gamlath R, Wimalaratna H. An unusual case of recurrent Guillain-Barre syndrome with normal cerebrospinal fluid protein levels: a case report. BMC Neurol. 2016 Sep 5;16:161.

Centers for Disease Control. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices – United States, 2018-19 Influenza Season. Recommendations and Reports. MMWR. August 24, 2018. 67(3);1-20. Available from the Internet at: https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm (cited 9/24/18)

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital