Notes on GBS and CIDP

These are my notes on some of the talks given in November 2008 at the Symposium. Please note the Disclaimer at the top of the thread.
_________________________________________________________________
[B]Life issues with GBS and CIDP[/B]

[B]Pain[/B]
This is much under-recognized and under-treated feature of GBS/CIDP.
Reports say between 15 to 85% of people have this. Probably 50-60%.
The wide variation in reports is likely because this is not a question asked enough, there is variability, and there are a lot of other vital things to worry about at the time like breathing. It also probably indicates how poorly understood pain in GBS is.

[B]Pain can occur at four times.[/B]
1.Pain can occur at the same time as the paralysis/weakness or even predate it.
In as many as a third to half of the people, pain may be the first symptom.
The initial pain is nociceptive– not neuropathic. This means it is like regular post-operative-like pain, not like the latter burning pain of neuropathy.
It can happen in the lower back, hips, and bottom and seems like a deep, aching pain that sometimes is associated with cramping or stiffness. The pain is typically not severe and is often proportionate to the weakness. This kind of pain typically peaks in a few days to a week. The treatments of choice are traditional pain medications. One needs to be careful about narcotics if there is a good deal of autonomic instability or respiratory compromise. This has to be balanced with the fact that it hurts and that pain causes additional autonomic instability itself. Steroids will not help the GBS but can be of benefit to the pain, if used judiciously.
2. Pain can occur as a consequence of immobility.
The best ways to help this are to minimize pressure—perhaps with an egg-crate or air-mattress, to do frequent changes in position, and to do physical therapy.
3. Pain can change or worsen as the paralysis improves
This is more likely due to axonal damage. It also is typically proportional to the weakness. It is different from the above kinds in that it occurs in the periphery (feet and hands) and seems to be more on the surface rather than deep. It is also typically described as burning, tingling, hot or cold. It can be worse at night or after exercise during the resting phase.
4. Pain can occur or change in association with rehabilitation.
This is typically the classic neuropathic pain.

[B]Medications for pain[/B]
Neurontin (gabapentin) or Lyrica (pregabalin)
Cymbalta (duloxetine). This is FDA approved for diabetic neuropathy, but it was said that it can definitely help some people with GBS/CIDP.
Other serotonin/norepinephrine reuptake inhibitors such as Effexor (venlafaxine)
Tricyclic antidepressants—amitriptyline, nortriptyline, desipramine, etc.
Combinations may work when single drugs do not. This physician said one of his choices is Cymbalta and neurontin. Another combination talked about was amitriptyline and oxycodone and gabapentin.
Narcotics—especially longer acting ones like oxycontin.

[B]Emotional pain.[/B]
This can be significant. There is often fear of loss of control, fear of dying and fear of relapse/recurrence. ICUs are not the best at personal dignity maintenance. Often there is depression because of life changes and alterations and stressors in the structure of the support system.

There was discussion as to why pain is worse at night. This may be, in part, due to distractions in the day and greater fatigue at night, but it also may be affected by body steroids and body changes at different times of the day (circadian rhythms).

There was discussion about cold feet. The most important first thing to figure out is whether the feet are really cold to another persons touch as sometimes they may not be actually cold in temperature, but just feel that way to the person with the neuropathy.

[B]Fatigue[/B]
This is a much under-appreciated part of GBS and CIDP but seems to occur in the majority of people if asked.
This is extreme tiredness and weariness.
Fatigability is slightly different—in this the more that is done, the harder it is to do it.

There are several potential causes and one should think about all of them and address the relevant ones.
Increased energy requirements in a demyelinated axon. Demyelinated nerves are ineffective in conduction nerve impulses—it takes a lot more energy.
Neurologic fatigue resulting from a weakened body (brain, nerves, neuromuscular junction, and/or muscles)
Inflammation and pro-inflammatory cytokines. ( This is a big reason that often one feels fatigued with the flu.)
Pain
Respiratory compromise
Deconditioning (weakness from lack of use of muscles after being paralyzed or bedridden.)
Central fatigue (in the brain). This is rare in GBS/CIDP, but classic for MS
Depression
Medications
Sleep disorder
Other coexisting medical concerns—infection, diabetes, thyroid problems, heart, or kidney problems, etc.

Modafinil may be of benefit. It is expensive. Amantadine does not help in the fatigue of GBS/CIDP—only central fatigue.
Consider changes in medications and treat other illnesses.
Treat pain and depression.
Consider a sleep study with specific treatment based on results
Supervised PT and careful exercise.
Energy conservation and planning of activities of the day.

[B]When to rest[/B]
There was discussion about whether to keep working if fatigued or to rest. It was answered that this is complex. One will feel better in the short term if you rest, but the goal is to get stronger, so one has to push a little to keep making steps forward. It helps a lot to have a physical therapist with experience to help.

The goal is the best quality of life possible and feeling terrible from overexercising will not help recovery. It is not expected to worsen the GBS, but it will impede progress toward recovery. One physician said the typical saying is “no pain, no gain”, but in GBS, the saying should be “Pain, no brain”. It is better to do little bits often than to over tire.

The indications of fatigue that should lead to stopping were
Recurrence/worsening of paresthesias
Muscles twitching (if this happens you did way too much—back up and do less next time)

[B]Finding a physical therapist that understands GBS/CIDP and the fatigue associated with them.[/B]
There was discussion to ask at rehabilitation hospitals, to look for physical therapists that are neurologically certified specialists (NCS), and to ask the physical therapists about their experience. The same issues are relevant in MS and myasthenia gravis as in the rarer GBS and CIDP, so the physical therapist might have experience with MS patients.

Exercise clearly improves recovery and helps decrease disability and fatigue.

[B]Yoga[/B]
There was discussion about yoga especially “senior” yoga that might be good for people with neurologic problems because many of the exercises are modified to be less strenuous.

[B]Shoes[/B]
There was discussion about shoes. A few audience members advocated rocker bottom shoes to help push off the foot to compensate some for foot drop. Two companies mentioned that make these are Dansko (available at theWalking Company) and MBT (available on the web).

[B]Sexual issues[/B]
It is important to realize that the greatest sexual organ is the brain and how one feels about oneself and your body. Features associated with GBS/CIDP that may affect sexual intimacy are weakness, sensory loss, pain, fatigue, sadness, changes in the family structure, and some medications.
Things that may help are communication with your partner—focusing on the positives not the negatives, positioning such as support with pillows to reduce energy needed, resting, timing, and planning. If one can only do a limited number of things in a day, one has to choose what gets priority and do extra resting in preparation for activities that need greater energy expenditure.

There was a survey of about a hundred patients with GBS. Most were young, more than 2 years after diagnosis, and the majority had had reflexes return. Still ¾ reported residual weakness and even more disability. About 40% had sexual dysfunction in their sustained relationship and this was not due to depression or stress in the relationship. Discussion of this will be clearer when it is published which should be soon.

Please note the disclaimer at the top of the thread.

[B]Immunizations[/B]
This was a topic of considerable debate and discussion. The discussion was this. The only major link with immunizations and GBS was with the swine flu shot. This was a somewhat unique situation in how the virus was produced for the swine flu vaccine. GBS occurs after other immunizations, but it is not 100% sure that this has a cause-effect relationship or just that uncommon things happen as well in a population in which a common thing happens. This being said, there are pretty convincing cases of people getting GBS after a flu shot and occasional cases of people getting GBS a second time after another flu shot. It was said, not to keep getting them in that case! For the rest of the people with GBS, there is little evidence that the flu shot (if it was not associated with GBS the first time) will lead to GBS a second time. The discussion with flu vaccine is that each year’s flu vaccine is different than other years. There is a risk of relapse of GBS, but the exact risk is not known. One should be cautious about getting the flu vaccine again, but most neurologists that commented said that they recommend it.

One person’s recommendation was no immunization in the first year after GBS even if the GBS was not associated with a vaccine. After that, think about the risk and benefits and talk with your neurologist.

There was discussion that in CIDP, perhaps as many as 5% might have some worsening of symptoms after any vaccine, but only 1 person (in the 200 studied) had enough worsening to need to go to a hospital. There was discussion that many people with CIDP are weakened, debilitated to some extent, and have a relatively high risk of dying from influenza, so that the risk to benefit statistics are on the side of getting the flu shot for protection. Several times it was stated that for a general person to get GBS in association with the flu shot the risk is about 1 in 125,000 and the risk of older debilitated people dying of influenze is 1 in 1000. For CIDP, it was stated by one doctor that he recommends the flu shot if someone is weak especially in breathing system or immunosuppressed and that if there is any worsening, he adjusts the medications to keep the CIDP under control. One point to think about is that if CIDP gets worse (in likely contrast to GBS), a person is unlikely to be hospitalized on a vent. The changes in CIDP are not as great and often can be rapidly suppressed with adjustment in treatment.

There was also discussion that some of the bad press with immunizations was due to the old rabies vaccination which was made in rabbit brain. The newer rabies vaccine is grown in duck eggs, so there is considerable less risk of GBS.

There was also discussion about the timing of GBS after immunization. Most people said that the GBS needs to have happened within 4 to 6 weeks of the immunization to be considered associated with it. The CDC says 4 weeks.

[B]Emotional coping[/B]
Set realistic goals for each day—what can I do for myself today?
Try to accomplish goals one step at a time not in large blocks. You still get it done.
Be your own cheerleader.
Be kind to yourself.
Stay flexible.
Find what works for you.
Communicate with those around you what you need and want—they cannot read your mind.
Work to make people comfortable around you and the changes/disabilities you have in your life.
Realize that the whole family and support system is affected by your illness and that all of you need to heal.
Accept help and make connections with others.
Accept change as a part of living and that you do not have control over everything.
Honor where you are in the process as you go through it.
Take action. Act as if things were different and this can help it to be so.
Exercise and take care of yourself.
Think about assistive devices as ways to help you live your life and not to define who you are. For example, glasses do not define you, neither should a walker or wheelchair.

[B]Advocacy and communication.[/B]
Advocacy is complex. Talk to Ed Gdula before making press announcements or using the name of the GBS/CIDP Foundation.
There are 23000 people that have contacted the foundation and 160 chapters. If you write or call to the foundation, they will send you a handout about advocacy as well as many links to web resources for people with disabilities, etc.
_______________________________________________________________

Several of the speakers of these topics said that they would send their PowerPoint handouts to the GBS/CIDP Foundation for distribution if requested. This included handouts about physical therapy and assistive devices and equipment and Advocacy and resources for disability. If you would want this write or call the GBS/CIDP Foundation. If not, I have her email.
_______________________________________________________________

Special thanks to Drs. Parry, Lisak, Amstutz, and Ashury and Mrs Lisak, Mr Gdula, Rich, Fuerst, and Killicutt and Ms Zell as well as the many other experts that chimed in with answers to questions.

Please note the disclaimer at the top of the thread.

[B]Research and going forward in GBS and CIDP. [/B]

There is an international Inflammatory Neuropathy Consortium. In this, efforts to advance research in GBS and CIDP include
Cochrane reviews of existing data
A database of people having MMN
The PERINOMS project to get better measures of clinical change in patients
The EGOS project to grade outcome in GBS
Genomics and SNiP databases
SIDGBS: second dose of immunoglobulin in GBS trial to see if this helps those that do not respond adequately to the first course of immunoglobulin
Alumtuzumab trial.

The Cochrane Collection evaluates the medical evidence for practice activities in diseases. This is part of evidence based medicine. GBS and CIDP, being rare, do not have as many randomized controlled clinical trials as most prevalent diseases often do. The number of subjects at any place are limited and the variety in disease courses and treatments are considerable.

Many more clinical trials are needed especially in mild GBS, AMAN, the Miller Fisher variant and other variants, combinations of treatments, and other ways to alter the immune response. As well, better ways to classify and describe the neurologic features and severity of GBS and CIDP are needed and well as to classify response to treatments.

There was a survey of CIDP patients in 2007 and 2008 that will be published soon looking at other medical factors, characteristics, treatments, duration, benefits of treatment, and outcomes as well as socioeconomic impact. Some of this is reported in other sections.

There was a clinical trial in humans using methotrexate to help control CIDP and permit less immunoglobulin to be used. This trial was not successful by itself, but does serve as a pilot of the issues that need to be considered for other trials in CIDP particularly how to get the most uniform starting population, how to alter other treatments, how to measure outcome in an accurate and functionally relevant manner, etc.

There was an international clinical trial of interferon beta 1a. Unfortunately not nearly as many people participated as needed and there is missing data. It was also a short trial and this may not have been optimal.

Potentially promising agents that alter the immune response
Rituximab (Rituxan, anti-CD20) that wipes out B lymphocytes that make antibody.
Eculizumab and other monoclonal antibodies that affect complement.
Natalizumab a monoclonal antibody that affects integrins and thus cell migration as occurs with T lymphocytes.
Lamotriguin that alters the axonal depolarization by sodium channel blockage
Alemtuzumab (Campath, anti-CD52) that wipes out lymphocytes.
Infliximab that affects TNF alpha, an important effector molecule in inflammation.
IFN beta 1a

One of the presenters talked about an animal model for GBS in which one can study nerve damage caused by anti-GM1 and anti-GD1a antibodies. The presence of these bad antibodies delays nerve healing and leads to incomplete recovery. He has a mouse deficient in a central component of complement as well as one defective in the Fc gamma receptor also important in the activity of complement and can use these to study the effect of complement on the damage in CIDP.

One of the presenters talked about erythropoietin as protective of the nervous system in MS and in stroke. He is testing this in the lab using nerve cells in culture and there seems to be promise. The concern is that erythropoietin can increase the risk of blood clots and GBS can as well, so this might be an issue in clinical use. He said that chemical modification of the erythropoietin can still result in the nerve regeneration/repair but does not allow the molecule to increase the blood thickness in the same way that regular EPO does. This medicine will need to be tested in a live mouse model of GBS and then may can be tested in humans to see if it helps nerves to heal. _______________________________________________________________-
Special thanks to Drs. Hughes, Koshi, Gorson, Cornblath, Sheikh, and Ashbury as well as the many other experts that commented on research issues at other times. Their amazing efforts in this rare set of disorders need to be recognized.

I thought the suggestions made and listed in the emotional coping section were really good–especially these six, which I will kind of speak about and expand as they may apply. First, though, I think it is important to say that most of us feel discouraged and sad. GBS comes on like a bonk to the head with a sledge hammer and the amount of change in life is tremendous as well as its abuptness. It takes time for one’s brain to catch up with all this. I think lots of people struggle to keep positive. Second, it is important to say that pain is depressing and it is almost impossible not to be depressed if there is a lot of pain. It takes over your life–so the first thing for you to do is to find a neurologist that will help address the pain until it is better.
1. Find what works for you. Each person is different in what is important in life, in how they cope with change, and in how they are affected by GBS. A tiny suggestion is to spend a day thinking about your goals and concerns–not with an “I can’t do this anymore” attitude, but from either 1. I miss this a lot and how can I get this to work again in my life or how can I substitute to get the same pleasure or 2. how can keep this from happening? For example, if one of your pleasures in life used to be going to concerts or book club or religious service or whatever but it is too hard to walk to go there right now, can you get a wheelchair and go with a friend, or invite a few friends for your own small concert–with CD or music video–at home? i say this because to me the isolation from usual social activities and limitations in walking really make a difference and finding ways to re-people my world, although different, helped a lot. One of my worries was losing touch with friends and family–so I tried to make a point to call them and to ask about them and be excited about their lives even though mine was more different now. Sometimes kind people do not want to share their normal life with you after badness has happened to you or now that you cannot do that. I tried to let people know that I appreciated them and their normalness and it did not distress me (most of the time) that I couldn’t do things anymore–at least relative to losing touch. One of the people at the symposium talked about how worried she was about getting weak and that she addressed this by starting an exercise program (and PT). That she started doing 3 minutes at a time because this is all she could do, but she kept saying I am doing this to get stronger and kept working at it.
2. Communicate what you need and want. It is so hard for people to understand the changes and restrictions in energy and stamina after GBS, that most cannot know how hard it is to walk 200 feet. They also, thus, cannot know how to help. Let people know if it makes things much better if you are dropped off near the door rather than walking from the parking lot. Get a disability placard if you used to drive. I think one of the best things I learned at the recent symposium was how important it is for people to preserve energy whenever they can so that what they have to use can be used as “quality time” and people respond to the fact that they can help so that you have quality time with them–that it is special to be with them.
3. Be kind to yourself. I think this speaks for itself. I know I have spent a lot of energy with the “I used to could do this” stubbornness and the “I ought to do this” guilt. If it really will not make a difference in your day, drop it and don’t feel guilty about it. Really and truly, is it that important to make your bed each day? Probably not. So use your limited energy with what is important–talking to friends or family, doing work, seeing the baseball game of your son….
4. Set realistic goals. So much of life is filled with a lot of running around and busyness. If you cannot do much of what you used to do, what might you be able to do? Have you always wanted to paint or to learn to knit? You might have time to do this at this point in time and many of these type things do not take as much energy–although only you know your arm stamina. I think of this as a door closed–find window to open situation. It lets one do something that fulfills you and to think about something good coming out of a hard time rather than feeling sorry.
5. One of the suggestions was to act as if…. one feels better or as if one is not discouraged. If you work to show cheerfulness (even if it is hard), you will feel some of it and it will be easier the next time. Maybe more importantly, if you act that you are a strong person with limitations, you will feel a lot stronger and it will be easier for other people to associate with you than if you think of yourself as a series of limitations. Maybe this is acting as if life is moving forward under your own direction rather than “life is bad and I have no control over it.” It seems that one has to find a belief that life continues, then has to start acting as if this is the case, exploring options, and eventually it will be the case and you will have a way to better cope and to better live life.
6. Look for the humor in life. See, I have not for years made my bed every day, but now I have a good excuse! When I used to climb mountains, I would make time to stop to admire the view. So now with “mountain climbing” the stairs, I have had to stop midway up and I tell myself it is “to admire the view”! i tell people that elevators at work are a tremendous blessing–not for the obvious fact, but rather that one has to stop and wait for them and that rest is really appreciated in my life now!
Lots of words because this is important and it is something that I have thought a lot about as I struggled with it and tried to see the windows and the “can do”s in life. I also think some of my most repeated words this last year are “I think I can”–used for stairs, times when I have to walk farther than usual, and as the day goes on. I may be slow, but I am determined.
I hope that this helps.
WithHope for a cure of these diseases