Guillain-Barre Syndrome

We used to think of this as only being associated with the flu. But we know now that GBS can be associated with any insult to the immune system, known or unknown (unknown in up to 40% of cases!). Now that we know COVID-19 can present, especially early on, with neurological symptoms, we need to go deeper in to this topic. So far, I have not only treated several patients in the inpatient acute and home sub-acute settings with GBS, but I’ve also identified a new onset of GBS in a patient I was seeing for neck pain after a cold. The longer I practice, the more GBS I run in to and it makes it feel like it is more common than it really is. But the actual incidence is 1-2 in 100,000. That’s pretty typical, to have your bias influenced by your experience. I always feel like everyone I see over the age of 70 needs to have a walker or cane to be safe, because those are the people I typically see for therapy, but we all know that isn’t the case in real life.

Like I started saying, GBS is one form of acute inflammatory demyelinating polyneuropathy (AIDP) which can be brought on by an insult to the immune system. For a refresher, the myelin sheath on a nerve is what promotes saltatory conduction, the process by which we can transmit neurological impulses so quickly throughout our nervous system. GBS typically takes between 3 days and 6 weeks to present after a respiratory or gastrointestinal system infection (that’s a large time-span, I know). I’ve also seen patients with GBS after a cold, the flu, or a tick bite. Guillain-Barre Syndrome can also be triggered as a reaction to a new drug. Make no mistake, even though some cases can be minor, new onset is a medical emergency.

Some diagnoses require you as a clinician to be more vigilant in your screening and ongoing monitoring for GBS symptoms, as they are more regularly associated with onset of GBS. These include:

• Campylobacter jejuni infection (GI infection)
• Haemophilus influenza infection
• Mycoplasma pneumoniae infection
• Epstein–Barr virus (Mono)
• Cytomegalovirus (CMV)
• Hepatitis (Especially Hepatitis E)
• Influenza virus
• Possibly COVID-19???

There is no known cure, although treatment with intravenous immunoglobulin (IVIg) and plasma exchange can decrease the length of symptoms. Some patients (25-30%) will require mechanical ventilation as the ascending demyelination progresses to their phrenic nerve and higher, resulting in diaphragm paresis/paralysis and ultimately ARDS. Cranial nerves can also become affected by GBS.

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So what do you need to be on the lookout for?

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Most patients develop sensory symptoms first. This is an ascending demyelination, so symptoms tend to start most peripherally. Sensory changes in the fingers or toes are most common. As sensory changes progress cranially, motor deficits begin to present. The real trouble that most people run in to is when the demyelination reaches their phrenic nerve, as this is the point they lose diaphragm control and are no longer able to breathe independently. As you saw above 25-30% of patients with GBS reach this point and require mechanical ventilation. The demyelination doesn’t necessarily stop there and not everyone responds to IVIg. And then we wait. We just wait until the demyelination stops.

Now, this is the typical presentation, but that doesn’t mean you can dismiss other odd symptoms. Like I mentioned above, I was seeing a patient in the home for neck pain and difficulty walking. I was thinking some major spinal insult at the time or a stroke, but her symptoms changed at every visit. Some days she could walk just fine with a cane, other days she could hardly stand. She had no sensory deficits at all and her neurological screening was unremarkable. She only had mild proximal lower extremity weakness. When I started seeing her, repeated cervical retraction actually improved all of her disabilities, including her leg strength, so I chased that rabbit. We went from non-ambulatory to walking without deviation in one visit.

It wasn’t until the fourth visit that she started reporting sensory changes in her thighs. I thought this seemed odd, but her light touch was diminished. I scheduled some extra visits and decided to see her the next day to assess changes. Huge bells were ringing but she continued to respond to mechanical interventions and I had nothing concrete, just gestalt. The next day, she had no light touch in her thighs (no dermatomal pattern) and she reported paresthesias in her groin, along with new onset of urinary incontinence overnight. This was the moment. This was when I realized not just how bad this was but WHAT this was. The red flag had finally waved. The kicker was that she STILL responded to mechanical interventions!!! Repeated cervical retraction STILL improved her function!!!

But no matter, I had realized what this was and I knew I had to get her to a hospital ASAP to slow the progression and provide her with ventilatory support if needed. I called the PCP and reported an ascending paresthesia with intermittent paresis and paralysis of atypical presentation three weeks after a cold and her reaction was immediate. Between the PCP, the nurse, and I, we got the patient direct-admitted to the hospital within the hour. The CSF specimen obtained from a lumbar puncture showed a result consistent with GBS. I picked her back up for home therapy four weeks later. She hadn’t progressed to a vent, thankfully, but she was in the hospital and rehab that whole time.

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Patients are now experiencing neurological effects of COVID-19 before, during, and after hospitalization for treatment. They may have even been experiencing them before we realized COVID-19 was the cause. From encephalopathies to ischemic strokes, the neurological complications are becoming more clear and the rehab community is jumping in to action. If you were practicing prior to COVID-19 and you didn’t do much treatment for cardiopulmonary conditions, your neurological skills may now need to be front and center.

The numbers are climbing. There are now several reported cases in Italy and the US where patients with COVID-19 develop GBS. Two new cases have even come forth in children (as of July, 2020). Some considerations are also being given to the presence of GBS as part of the initial respiratory failure. As COVID-19 can be present for up to 14 days without symptoms, that gives GBS more than enough time to develop (the 3 day to 6 week window after infection). According to the physicians who identified these cases in Italy, GBS onset was between 5 and 10 days after the first COVID-19 symptom presented (significantly before PICS should be considered).

Some physicians have asserted that GBS may be copresent during the rebounding phase of COVID-19 when patients are still on mechanical ventilation but progressing back toward functional respirations. Some patients present with a regression of respiratory function during this time that may be due to GBS, but the patient is sedated and heavily medicated and ICUAW may already be a factor so paresis is not a reliable indicator. If chest radiographs are clearing but respiratory function is declining, GBS should be a strong consideration. This also means that it may be seriously under-reported in patients with COVID-19, as it may appear as if the patient is regressing or failing the ventilator.

Where we may run in to some complications with treating GBS in patients with COVID-19 is if they have pre-existing contraindications for the effective interventions. For example, if someone has an active infection persisting (like the SARS-CoV2-19 virus for example) they cannot utilize plasma exchange. The same is true if they have issues with hemorrhage or clotting deficiency which we know can be an issue with COVID-19. Patients cannot utilize IVIg therapy if they have renal failure. We know that around 30% of patients with COVID-19 experience renal failure requiring dialysis support. So even if we can distinguish between side effects of COVID-19 and new onset GBS, we may not be able to do anything about it. This would significantly extend the length of recovery time.

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Speaking of recovery…

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That’s really where we come in, isn’t it! Guillain-Barre comes with a host of neuromusculoskeletal impairments and functional limitations that require skilled rehabilitation. You can imagine that when neurological signals are slowed down significantly, our internal communication system literally bogs down, all the end organs just don’t function properly. You can expect your interventions to target (at minimum):

• Sensory deficits, specifically proprioception
• Balance impairments in seated, standing, and dynamically
• Overall lowered functional status
• Impaired trunk control

Let’s start off by performing a neurological baseline assessment here. You have to figure out where you are starting from. Talk to your patient about their goals, what they need to get home, what they want to return to doing, and build on that. The Berg Balance Scale, although not my choice balance assessment, is the most studied in recent GBS research, and correlates with other testing. But perform what tests you think are most meaningful to your patient, reflect their true functional deficits, and include items that they are required to do in their normal life. If they are still at a seated level of function in acute rehab, the FIST is a great tool to start with. But you can also do a full-system assessment with the BESTest in any setting. Also keep in mind that you may need to do some testing for the cardiovascular system, like an aerobic capacity test, if your patient also has COVID-19 (or just had influenza or pneumonia or any other respiratory insult).

When it comes to strengthening, you have to consider the neurological anatomy that has been damaged. We know it takes nerves forever to regrow after damage, and that’s after Wallerian degeneration has completed. In GBS, the full nerve structure has not been damaged, just demyelinated. But this still will take a while to heal, especially in the presence of a hypoxemic comorbidity, as reduced overall tissue oxygenation also affects the neurological system. So strengthening should be focused on functional tasks and monitored closely as the patient can be expected to fatigue quickly due to poor recruitment. We usually hear that you should avoid eccentric exercises in this population for this reason. High-Intensity exercise was shown to improve outcomes across all systems relative to lower intensity exercise in patients with GBS. However, there is very little well-controlled research for interventions for these patients.

In the long term, rehab is indicated and expected to take place over an extended period of time with GBS alone. Very recent research has shown that physical therapy interventions are most successful if provided for greater than six months with patients who have experienced GBS. When you factor in a respiratory virus and subsequent sequelae (like the effects of mechanical ventilation or PICS), we can expect a long return to function time frame. Set your patient up for success by setting achievable and reasonable goals. Break your time frames down and try to achieve goals every week and make sure your patient KNOWS they are achieving goals and making progress. The road is long, but the news is good! 85% of people with Guillain-Barre Syndrome make a full recovery.

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What is your favorite strengthening exercise to use with patients who have had Guillain-Barre Syndrome? Tell me about it in the comments!

References

Arsenault, N. S., Vincent, P. O., Yu, B. H. S., Bastien, R., Sweeney, A., Zhu, S. (2016) Influence of exercise on patients with Guillain-Barré Syndrome: a systematic review. Physiotherapy Canada. 68(4):367-376. https://www.utpjournals.press/doi/abs/10.3138/ptc.2015-58

Head, V. A., & Wakerley, B. R. (2016). Guillain-Barré syndrome in general practice: clinical features suggestive of early diagnosis. The British journal of general practice : the journal of the Royal College of General Practitioners, 66(645), 218–219. https://doi.org/10.3399/bjgp16X684733

Huzmeli, E.D., Korkmaz, N.C., Duman, T., Gokcek O. (2018). Effects of sensory deficits on balance, functional status and trunk control in patients diagnosed with guillain-barre syndrome. Neurosciences. 23(4):301-307. doi: 10.17712/nsj.2018.4.20180098.

Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EFM. (2001). Anticipating Mechanical Ventilation in Guillain-Barré Syndrome. Arch Neurol. 58(6):893–898. doi:10.1001/archneur.58.6.893

Mayo Clinic. (2020). Guillain-Barre Syndrome Overview. Retrieved from https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/symptoms-causes/syc-20362793

Prada, V., Massa, F., Salerno, A., Fregosi, D., Beronio, A., Serrati, C., Mannironi, A., Mancardi, G., Schenone, A., Benedetti, L. (2020). Importance of intensive and prolonged rehabilitative treatment on the Guillain-Barrè syndrome long-term outcome: a retrospective study. Neurol Sci. 41(2):321-327. doi: 10.1007/s10072-019-04077-x. Epub 2019 Oct 4.

Sharshar, T. (n.d.) Guillain-Barre Syndrome. [Presentation]. University of Versailles – Saint Quentin en Yvelines, Raymond Poincare Teaching Hospital. [French Neuro-Anesthesia and Resuscitation Association]. Garches, France. Retrieved from http://www.anarlf.eu/medias/slideshows/fichiers/GBS-DIU-Lyon-2015.pdf

Toscano, G., Palmerini, F., Ravaglia, S., Ruiz, L., Invernizzi, P., Cuzzoni, M.G., Franciotta, D., Baldanti, F., Daturi, R., Postorino, P., Cavallini, A., Micieli, G. (2020). Guillain–Barré Syndrome associated with SARS-CoV-2. NEJM. Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMc2009191

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