What is Guillain-Barré Syndrome (GBS)?

One of my most memorable encounters as a medical student was with a patient I met on my very first clinical attachment. I was a fresh-faced ‘third-year’, only recently let loose onto the wards, and keen not only to learn the clinical medicine but also to give time to my patients’ stories; I felt it was important to learn what it feels like to be a patient.

Shaun stood out among the other patients on the respiratory ward, who were old and mostly there because of smoking-related lung conditions. Shaun, a 27-year-old primary school teacher, was neither old, nor a smoker, but was easily the most critically ill patient under our care.

He told me that at first, all he noticed was a tingling in his feet, which slowly moved up his legs. The following day, the odd sensation had reached his knees, he realised he was having difficulty walking. By the time he’d seen his GP, been sent to A&E and reached our ward on the second floor and could barely move his legs at all and his hands had had become weak too. He was warned that the weakness and tingling would continue to progress up his arms and body, and that if it reached the level of his neck, his diaphragm and muscles of breathing might become involved. The respiratory doctors were getting him to do regular breathing tests to monitor the this, but if things progressed much further, he may have to go to the intensive care unit to have a tube placed into his lungs and his breathing taken over by a machine. Terrifying, especially for someone who was previously so fit and well.

This is Guillain-Barré syndrome (GBS) and, fortunately, it’s relatively rare (it affects 1-2 in every 100,000 people per year).

However, the number of cases being reported in Latin America shot up, at the same time as the outbreak of the Zika virus. The increase was about 2-10 times as many cases as usual, depending on which country you look at.

What is Guillain-Barré syndrome?

GBS is a condition affecting the nerves which communicate between the spinal cord and the muscles of the limbs. Longer nerves tend to be affected first, hence weakness affects the lower leg before the upper leg and the hands before the upper arms.

The symptoms usually progress over the course of around 2-4 weeks, after which there is a plateau phase, where the weakness may persist for several months. A spontaneous recovery eventually occurs, but some patients are left with some residual weakness and never get quite back to normal.

gbs graph.jpg
Time course of GBS. Following an infection, the body produces antibodies to ‘gangliosides’ which attack the protective lining of the patient’s own nerve cells. Symptoms of GBS therefore, only begin around 2-4 weeks after their initial infection but may last for months. Even after ‘recovery’, there may be residual disability.

The muscles responsible for breathing may eventually be affected, which may result in patients needing to go to the intensive care unit for mechanical ventilation. The nerves which control the heart can also become involved, causing problems with blood pressure and abnormal rhythms of the heart, which is another common reason for patients to require intensive care.

Make no mistake, this is a serious illness. Terrifying for the patient, and fatal in 2-10% of cases.

ventilated pt.jpg
Many patients with GBS end up on a ventilator: a horrible experience

What causes Guillain-Barré syndrome?

GBS most commonly occurs following an infectious illness, such as diarrhoea or a chest infection, typically around 2 weeks after the body has fought off the infection.

Shuan’s GBS started a couple of weeks after a bout of food-poisoning (likely due to a diarrhoea-causing bacteria called Campylobactor, which is a particular culprit for triggering GBS), but various infections, (including the Zika virus) have been shown to trigger the condition.

Why does this happen?

It’s thought that certain proteins on the surface of an invading bacteria or virus can look very similar to a protein on the lining of our nerve cells. Most of the time this doesn’t cause problems, but occasionally the body’s immune system, after launching an attack against the infection, gets confused and begins to attack our own nerve cells as well, resulting in the GBS symptoms.

gbs diagram
In GBS, the body’s immune cells (macrophages and lymphocytes) destroy the protective ‘myelin sheath’ around nerve cells, mistaking it for an invading bacteria or virus. This prevents nerve impulses reaching the muscles, which fail to contract, resulting in paralysis.

How do you diagnose GBS?

Our diagnostic tests involve doing a ‘lumbar puncture’ to sample some of the fluid which surrounds the spinal cord. We also do ‘electrophysiological tests’, placing electrodes on the limbs and passing tiny currents to test the conduction of the nerves. We might also do some blood tests to look for a specific infectious trigger or exclude other infections and toxins which can cause similar neurological symptoms.

Diagnosis can be tricky, because the lumbar puncture and nerve conduction studies might come back as equivocal and sometimes we have to settle for a diagnosis of ‘probable GBS’.

Additionally, there’s no way to definitively prove that a patient’s GBS was due to a specific infectious cause, such as the Zika virus. The best we can do is to prove that they have had Zika virus recently and then some days later developed GBS.

Are there any treatments?

Patients with GBS will receive general supportive care and careful, regular monitoring of their neurological symptoms. This involves regular breathing tests to check that their muscles of respiration are not becoming affected.

We have a couple of specific treatments which slow and may even halt the progression of the paralysis, but they don’t work every time and are extremely expensive.

The first of these, called ‘IVIg’, involves giving ‘antibodies’ derived from healthy human blood, which stops the problematic immune response that the patient’s immune system has mounted against their own nerves. IVIg costs around £5,000-10,000 for a single course, and often more than a single course is needed.

The second treatment, called ‘plasma exchange’ requires the patient’s blood to be passed through a machine so it can be cleared of all the harmful proteins before being returned to the patient’s circulation. This is even more costly than the ‘IVIg’ treatment.

As a result of their cost, neither of these are particularly accessible in the majority of countries which have been affected by the Zika virus outbreak.

~~~

GBS is a serious and scary illness. It’s difficult to diagnose and expensive to treat. The countries being affected by increased numbers of Zika-GBS cases are generally poor and already suffer from limited healthcare resources, which only adds to the tragedy.

Hopefully this has given you a bit of an insight into why our team at ZikaPLAN, as well as other researchers from all over the world, are trying so hard to better understand and develop treatments for this terrible illness.

Next up: I’ve written about what we know about the link between Zika and GBS.

~~~~~~

Further reading:

A review article on GBS. For those with a scientific or medical background looking to learn more, this is probably the most authoritative review article on GBS, and it’s recent (Feb 2016), so it’s up to date. It also just so happens to be written by some of the principal investigators in the ZikaPLAN and IGOS-Zika teams i.e. my bosses!

 

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s