Dr. Kenneth C. Gorson, MD
President Elect GBS|CIDP Foundation International Global Medical Advisory Board
Guillain-Barre syndrome (GBS)
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Medical Research: What is Guillain-Barré Syndrome? What are the main symptoms?
Dr. Gorson: Guillain-Barré Syndrome (GBS) is an immune mediated disorder affecting the peripheral motor and sensory nerves and nerve roots, and is the most common cause of rapidly progressive generalized paralysis in western countries. It is characterized by acute or subacute, progressive, symmetrical limb weakness with distal numbness or tingling in the arms and legs, and reduced or absent deep tendon reflexes in previously healthy patients. Patients notice the sudden onset of difficulty walking, climbing stairs, carrying objects and impaired fine motor skills. Balance is impaired due to sensory loss or weakness and a minority of patients develop facial weakness, trouble speaking and swallowing, and double vision. Severely affected patients may require ventilator support due to respiratory muscle weakness. Symptoms worsen over days to weeks, and most patients reach a maximum deficit (nadir) by 4 weeks, followed by a plateau phase for weeks to months, and then a recovery phase over additional weeks to months. Approximately 80 percent of patients recover to walk with minimal or no residual symptoms or functional disability. Maximal improvement usually occurs by one year, but more severely affected patients may continue to observe subtle improvements for several years after symptom onset.
In approximately two thirds of affected patients there is some preceding triggering event, classically a viral syndrome manifest as a transient upper respiratory or gastrointestinal illness with fever that resolves uneventfully prior to the onset of the neuropathy. Current evidence indicates the pathophysiology of GBS is related to molecular mimicry, where the patient’s antibody response to the preceding infection interacts with a variety of antigens on peripheral nerve myelin or axons producing a generalized but multifocal inflammatory demyelinating process and associated axonal loss in some instances.
The diagnosis is established with nerve conduction studies and electromyography, which shows features indicative of a demyelinating neuropathy affecting multiple motor nerves in the arms and legs. The cerebrospinal fluid protein level is elevated without a cellular response (cyto-albuminological dissociation) in up to 80 percent of patients when performed in the first week of the illness.
Treatment is directed toward the immune response, and several large randomized controlled trials have demonstrated that intravenous immunoglobulin and plasma exchange hasten recovery, and both treatments have similar efficacy.
Medical Research: How is the Zika virus possibly related to Guillain-Barré Syndrome, CIDP?
Dr. Gorson: There is currently an epidemic of Zika virus infection in Central and South America, and there has been a several fold increase in the incidence of Guillain-Barré Syndrome in parallel with the Zika virus outbreak. In Bahia, Brazil, in July of 2015, 62 percent of patients afflicted with Guillain-Barré Syndrome had symptoms consistent with previous Zika infection (mild fever, skin rash, conjunctivitis, muscle or joint pain, and general malaise that begins 2-7 days after the bite of an infected mosquito). One possibility may be that the Zika virus could be a preceding infectious trigger to GBS, but this relationship has not yet been proven and will require careful epidemiological studies to confirm a definite association between Zika infection and Guillain-Barré Syndrome.
Medical Research: What should clinicians and patients be aware of?
Dr. Gorson: Clinicians should be familiar with the symptoms of Zika infection. Blood tests can help to confirm the diagnosis. Some (virological PCR tests) are useful in the first 3-5 days after the onset of symptoms, while others (serological tests) detect the presence of antibodies but are useful only after five days. Patients who live or have traveled in endemic areas who develop symptoms of Zika infection should seek care with their health care provider. Patients who develop any sudden and progressive neurological symptoms suggestive of Guillain-Barré Syndrome that develop after suspected Zika infection warrant prompt evaluation in emergency department with neurological consultation. Clinicians should be aware of a possible link between Guillain-Barré Syndrome and Zika virus infection.
Medical Research: What recommendations do you have for research as a result of this link?
Dr. Gorson: There is an ongoing, prospective international trial of Guillain-Barré Syndrome, collecting clinical, laboratory, electrophysiological, treatment and outcome data as pre-specified time intervals from the initial presentation through at least one year follow-up, the International Guillain-Barré Syndrome Outcomes Study (IGOS). Serum samples have also been collected to allow for testing for the presence of antibodies to a variety of preceding infections. There are currently 144 centers from 18 countries participating in IGOS, and clinicians in Brazil are currently organizing to participate in IGOS. One research objective will be to test the serum collected from GBS patients for Zika virus infection and compare the findings to control patients to determine the nature of any potential association between Zika virus and GBS. If an association is demonstrated, additional data can be analyzed to determine if there are any specific clinical features, treatment response and outcome in GBS patients previously infected with Zika compared to other Guillain-Barré Syndrome cases.