When Is the Clinical Nadir for Guillain-Barré Syndrome?

Patient Presentation
A 6-year-old female came to clinic with a 3 day history of abnormal gait. Her mother said she seemed to be walking funny and was having more problems going up stairs.
She said she felt a little unbalanced but denied any vertigo. She also denied any pain, fever, chills, nausea, emesis, diarrhea, cough, rhinorrhea, rashes, vision changes or breathing problems. The mother said she was able to do other things but seemed a little more tired. The past medical history showed she was treated as an outpatient for community acquired pneumonia 1 month previously. She was otherwise well and was completely immunized. The family history showed no neurological diseases but there was thyroid disease and diabetes on both sides of the family. The review of systems was otherwise normal. There was no travel history and no known tick bites.

The pertinent physical exam showed a well-appearing child. Her vital signs were normal without tachycardia, blood pressure changes or fever. Her growth parameters were normal. Heart and lungs were normal. Her neurological examination showed normal mentation. Cranial nerves III-XII were normal. She had normal strength and deep tendon reflexes in her upper extremities. In her lower extremities she was able to lift her legs against gravity but not against pressure. Ankle reflexes could not be obtained and knee reflexes were decreased bilaterally. She said her legs felt a little funny but there was no discernable level where she had changed sensation in her legs. She was able to sit without support. She had a slightly halting gait and a positive Gower sign. No skin changes were noted. She had good peripheral pulses. The laboratory evaluation in the clinic showed a normal respiratory peak flow.

The diagnosis of an acute onset of lower extremity weakness and areflexia was made. Guillian-Barré syndrome was considered the most likely cause as the patient was afebrile and had recent community acquired pneumonia. After discussion with a pediatric neurologist, the patient was transferred to a regional children’s hospital where her clinical course showed she underwent several tests including neuroimaging which showed no spinal cord anomalies and a lumbar puncture that had increased protein and 8 lymphocytes. The patient had ascending paralysis of the lower extremities over the next 2 days up to her hips and was treated with intravenous gamma globulin. The patient improved slowly and was monitored closely and never had any respiratory compromise. She was discharged on day 10 to a local relative’s home and she was monitored daily for the next few days. Her symptoms continued to improve and by 6 weeks the family denied any problems and her examination was normal.

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 prodromonal gastroenteritis or respiratory illness. It is most often associated with Campylobacter jejunae, Haemophilus infuenza, Mycoplasma pneumoniae, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus. There are some possible associations with GBS and influenza A vaccination but it has not been associated with other vaccines. 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. Surgery may also trigger antibody production.

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.

There are a number of variations of GBS. The classic form is acute inflammatory demyelinating polyneuropathy (ADIP) and ADIP is about 75% of cases especially in the US and Europe. Acute motor axonal neuropathy (AMAN) is similar but has no sensory defects and has more fulminant motor defects. Miller-Fisher syndrome is another variant that has ataxia, ophthalmoplegia and areflexia without peripheral weakness. The other variations have different sensory deficit profiles.

The differential diagnosis of paralysis is large, but important ones for GBS as they are treatable include botulism (which is a descending paralysis), acute spinal cord problems such as cord compression or transverse myelitis (usually has a spinal cord level on examination), and tick paralysis (which improves after the tick is removed). Diagnosis is clinical but elevated cerebrospinal fluid protein without an elevated cell count, usually < 10 cells/mm3 and all or most are lymphocytes, is the most common profile.

Treatment is supportive. The nutrition, respiratory support, rehabilitation and psychosocial needs of the patient need to be met. Patients are usually monitored in the hospital especially for the risk of respiratory failure. Immunoglobulin (IVIG) is felt to bind the autoantibiodies and downregulate antibody production. IVIG helps to improve ambulation and decrease hospital stays. Dosing is usually a total dose of 2 g/kg that is divided over 2-5 days. Plasmapheresis decreases the levels of autoantibodies that are circulating and may also decrease cytokines. It can be performed in patients > 10 kg but obviously has additional problems of being more invasive than IVIG. Both IVIG and plasmapheresis have not shown differences in long term outcomes.

Learning Point
The clinical nadir when symptoms are the worst is usually around 2 weeks after symptoms begin and most patients begin improving after that. Most have signficant improvement by 4 months and most have full recovery. Patients with classic AIDP or AMAN usually recover more quickly than other variations. Some still have problems including fatigue and sensory issues long term. It is uncommon but GBS can occur more than once.

Questions for Further Discussion
1. What are indications for referral to a neurologist?
2. What are potential radiologic imaging studies which may help with the diagnosis for GBS?
3. What causes ataxia? Click here for a differential diagnosis.
4. What causes muscle weakness with and without hypotonia Click here for a differential diagnosis.

Related Cases

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

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.

Rosen BA. Guillain-Barre syndrome. Pediatr Rev. 2012 Apr;33(4):164-70.

Ryan MM. Pediatric Guillain-Barre syndrome. Curr Opin Pediatr. 2013 Dec;25(6):689-93.

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.

Sudulagunta SR, et. al.. Guillain-Barre syndrome: clinical profile and management. Ger Med Sci. 2015 Sep 21;13:Doc16..

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