Notes of CIDP

    • Anonymous
      November 15, 2008 at 10:52 pm

      These are notes on the many discussions on CIDP at the 11/08 Symposium. Enjoy and May the force of knowledge be with you.

      First: Disclaimer to Many Things. Please note.
      1. None of these comments are medical management standards—the approach to care of patients with GBS/CIDP is just discussed as are some of the things just now making it to thoughtful consideration. There was discussion that specific information should not be attributed to a specific presenter because this might lead to misunderstanding.
      2. The writer is not a neurologist and not an expert in this field. Neither is the writer affiliated with the GBS/CIDP Foundation other than as a regular lay member of the discussion forum.
      3. The writer IS passionate about use of the internet to distribute to those that really need it understandable medical information especially about rare conditions for which there is little published or in textbooks. The internet is one of the most powerful tools to impact knowledge available to better educate and inform people of any level about innumerable topics. Please take this information with a grain of salt as you should all information on the internet. This information should not be considered as without error because the field is complex and there are many controversies. However, if nothing else, realize that there ARE a number of really smart people that do officially work with the foundation and are working hard to understand and to help people with GBS and CIDP. I am impelled to acknowledge them in groups for their amazing commitment to this rare illness.
      4. These notes were put into four groups for posting. Since the purpose is for people to understand what is being talked about, the terms need to be understandable, so some terms are explained in parentheses.


      [B]General information[/B]
      Prevalence (number present at any time) 2.8 per 100,000
      Incidence (number diagnosed in any year) 0.5 – 0.8 cases per 100,000 per year
      About 5000-15000 cases diagnosed per year in the US
      Twice as many males as females
      Peak incidence at age 60-70 years; average age in low 50s

      [B]Signs and Symptoms[/B]
      Often numbness and tingling in periphery (hands and feet)
      Loss of deep tendon reflexes
      Cranial nerve involvement is rare
      Rare to have enough effect on nerves to breathing muscles to need a ventilator
      54% need an aide to walk at some time in their disease

      Progression of neurological symptoms for more than 2 months or relapsing with slowed motor nerve conduction or conduction block
      About 10-20% monophasic (meaning getting worse and then better once)
      About a third progressive (meaning getting worse over time). This can be divided into steadily progressive and to stepwise progressive. (The former is typically slow steady worsening. The latter is stepwise worsening on top of a steadily worsening baseline so that one gets worse fast, then stays stable for a bit, then worsens again, but does not get better than at the start.)
      About half, relapsing (getting worse and then better repeatedly). Relapsing can be divided into progressive relapsing and relapsing remitting. (The former is getting worse and better in the short term, but over time cumulatively getting worse; the latter is getting worse and in the short term, but not as much difference in the long term.)

      [B]Tests used for diagnosis[/B]
      Motor conduction velocity < 70% LLN (lower limit of normal) on two or more nerves; conduction block, temporal dispersion, prolonged distal latencies and/or F waves in 2 or more nerves. CSF with high levels of protein compared with cells Nerve biopsy usually reserved for cases in which the medical history or other studies are confusing. Experts did not recommend doing it if the MCV or CSF or history were able to yield the diagnosis well enough. (Practically, there was discussion that one does not have to have the nerve biopsy in addition to supporting MCV and CSF, but that this is an alternative way to the diagnosis in complex cases.) [B]New and better diagnosis criteria[/B] Newer definition being developed; to be published in 2008. Authors will include Dr Koshi and Dr Cornblath. Sensitivity and specificity of new criteria both in 80s—better than any other criteria. (Sensitivity is the ratio of all those truly having the disease and testing positive for it divided by all that have the disease (TP/TP +FN). A sensitivity of 82-84% means that 82-84% of people having the disease will be found to have it. Specificity is the ratio of those testing negative truly divided by all that do not really have the disease (true negative/(true negative + false positive). A specificity of 88-90% means that 88-90% of those without the disease test negative for it by these criteria. Even by this criteria, about 16-18% of people having CIDP by the “gold standard” will not be diagnosed as having it. The important point for us is still that some people are going to be hard to diagnose, but this will be better than previous criteria. Hopefully, this will help those that are atypical or hard to diagnose by the previous criteria. It is important for specificity to be high because one does not want to treat someone for a disease that they really do not have.) With the new criteria, people with known other reasons for chronic neuropathy (such as diabetes, a paraprotein, or a hereditary neuropathy will be excluded. The remaining will need to have one or the other of the following, 1. More than half of the tested nerves being abnormal on either distal latency, conduction velocity, or presence of F waves. OR 2. Having a symmetric onset and exam as well as distal weakness in all four extremities with at least one extremity with proximal weakness. The specifics of the new criteria will be in the paper when published. [B]Discussion of time to diagnosis.[/B] In the Outcomes study (soon to be published), the time from onset of symptoms until diagnosis was on average about 24 months (range from a few days to 40 years) and half of the people were not diagnosed until after more than 6 months of symptoms. If people had more severe disease such that they were wheelchair bound, the diagnosis was made in all in less than a year and a half. The faster diagnosis can be due to a combination of the disease manifestations and a greater push to try to find out what it is because it is so severe. [B]CIDP occurring after GBS[/B] It was stated that about 3-5% of reports here have GBS converting to CIDP. In another country, this is up to 16%, but a rough pole of neurologist there seemed that the number was closer to the 3%.

    • Anonymous
      November 15, 2008 at 10:56 pm

      See disclaimer at the top of the thread.

      Treat the person (individualize to maximize function and quality of life for this person)
      Treat the disease to limit additive damage.
      Treat the Symptoms. It is hard to function well if in pain.
      Do not forget the impact that the illness has on work, social, and coping areas.
      (Treatment should be collaborative with neurologist, patient, and patient’s important people. One does not necessarily need to treat a stable numbness that does not impact function, but it is wise to try to treat a symptom that causes a huge impact on daily function in that individual’s life).
      Treatments for weakness can include medications, physical therapy, and assistive devices (AFOs/orthoptics, cane, wheelchair, etc). Treatment for pain can include medication, physical therapy, and surgical options (presumably ablation).

      [B]Goals of Treatment[/B]
      Return to normal health or function
      Improve function to the best possible
      Feel better
      Keep disease from getting worse.
      There was discussion that in some acute illnesses, one can return to normal health and function in life, but that sometimes in chronic illnesses, the best one can do is to improve function to the best place possible and limit the amount of damage caused by the disease. It was also discussed that feeling better in important and that helps function in life in greater proportion than expected from impact on the disease process itself.

      [B]Cure or Control[/B]
      IV IgG rarely cures CIDP, it just help control the amount of ongoing damage to the nerves.
      The immunosuppressive agents may foster remission and sometimes stable (prolonged) remissions, so they can be considered curative at time.

      [B]Treatment Options[/B]
      1 or 2. Steroids
      1 or 2. IV IgG
      3. Plasma exchange
      4. Immunosuppressive/cytotoxic drugs (cyclophosfamide, azathioprine, cyclosporine, mycophenolate, methotrexate, etc.
      (There was discussion that people should not be scared of using steroids due to concerns with side effects and that immunoglobulin can have significant side effects as well in some people. It was also discussed not to forget about trying plasma exchange is someone is really doing poorly and has failed or cannot take the two top therapies. It was also discussed that these three were the only scientifically (trial based) proven therapies to work, but that if they fail, the immunosuppressive/cytotoxic drugs can be used.)

      [B]Treatment Duration for CIDP[/B]
      Only one month in < 10% About 30% one month to a year About 30% 1.5 to 4 years About 30% more than 4 years Average 40 months, range 1 month to 40 years, median 24 months (median means that half the people were treated less than 24 months and half more than 24 months) There was discussion about how to know if a treatment works. In a study of the benefits of IV IgG, four measures were used, motor, balance, pain, and sensory with zero normal and 3 worst for each. The worst group (wheelchair bound) had the greatest benefit with more than 1/3 improving, but notably the improvement in this group was significant for the fact that 2/3 of these were able to walk again after treatment. (The conclusion from this was that people can get a lot of benefit from the treatment if they benefit and so one should try.) People that had less than a year of symptoms did better—it is postulated that this might be due to axonal damage that occurs the longer CIDP persists. As many as 80% of the people not have CIDP for a prolonged time improved. In the RMC=Randomized Methorexate CIDP trial in which the goal was to reduce the amount of IV IgG given, more than 40% of the people on placebo (inactive drug) in addition to immunoglobulin were able to reduce the amount of immunoglobulin needed for disease control. Methorexate was slightly better, but could not shown to be significantly different compared with placebo. There was discussion that a longer trial, a test of how dependent people really are on immunoglobulin, better measures of outcome, and higher doses of methotrexate might make a significant difference. There was comparison from a study of outcome done in the mid 1970s and to a recent study. In the old study, 11 % of people with CIDP died of it or complications from it and now only about 1% do. There was the same percentage—about 60% reported as disabled although the definition of this was different. Most impressive probably for the benefits of modern therapy are that almost 30% were confined to a wheelchair in the old study and only about 7% now and the converse set of numbers was applicable for those considered to have had CIDP resolved such that they were either recovered or not needing medications to remain stable. [B]Questions and Discussions on the Top three therapies.[/B] [B]Discussion about IV IgG[/B] There was discussion of how best to wean off IV IgG When start to wean, use signs and symptoms to guide weaning—want to not worsen before next dose—minimize the damage. Can wean either by decreasing the dose of IV IgG given or spacing out the interval between doses—both work. Patient factors help to guide which to do. There was discussion about how to know if IV IgG is working. Again want to not have any worsening before next dose—may need to increase dose or give the same dose more frequently. One expert says he treats aggressively until no more improvement occurs, and then slowly reduces the therapy intensity from that. This helps to stop the ongoing damage. There was discussion that IV IgG seems to work better in pure motor CIDP and both work in motor and sensory CIDP. [B]Discussion about steroids.[/B] One of the newer ways to treat CIDP is with pulse steroids and this is showing a lot of success with fewer side effects that continuous daily or alternative day steroids. Two main ways are more common. Ther first is with high doses of steroids (often decadron) given for four days every four weeks or month. The other is oral or IV steroids (typically prednisone or methylprednisolone) given once a week. It was stated that there was less weight gain, high blood sugars, and high blood pressures seen with this compared to the older ways. [B]Discussion about chronic plasma exchange. [/B] Not all people need an indweeling IV access in order to get pheresis. It depends on the person. Think about the risks of infection. If standard access devices do not work, a couple doctors said they had patients with a fistula as is used for hemodialysis. [B]Discussion about other therapies. Discussion on Azathioprine[/B] In over 300 people with CIDP in the Outcomes Survey in which many of you may have participated, azathioprine was used in about 13% of the people, about twice (2-4 times) as frequently as the other immunosuppressive agents. [B]Discussion on CellCept (Mycophenolate)[/B] There are two serious CNS risks to think about with the use of this medication—Lymphoma in the brain and PVL (periventricular leukoencephalopathy). These risks also occur with other immunomodulary medicines. It was discussed repeatedly that virtually all medicines have good things and bad things associated with taking them and that this medicine is not exception. It was stated that it is important to not fear a very small chance of a rare complication so much that one does not treat the large risk of ongoing nerve damage from CIDP if other options will not work. It was stated that all patients should discuss therapy option risks and benefits with their neurologist. [B]Less used Therapies Rituximab[/B] There was discussion about rituximab in CIDP and the general consensus was that it seemed about 50% of people benefitted from this medicine. It was stated that there is a paper in press that response is much better in CIDP associated with an IgM paraprotein. It was stated that rituxan is worth trying in CIDP if other treatments fail. [B]Discussion about bone marrow transplant for treatment[/B] There was concern in most that there is a serious risk of dying with this treatment and that it is really hard on the person. It was quoted that there are reported only about 6-7 cases of autologous (getting your own bone marrow back) BMT in the medical literature for CIDP and that there is concern that several patients have relapsed in about 2-3 years. Allogenic (getting rescue cells from someone other than yourself) stem cell transplant has a better chance of curing the CIDP, but the risk of dying from complications of the transplant are much higher. It was said that the chance of dying during transplant is higher in people with lupus or MS than in people with cancer. It was also said that people have seen return of the autoimmune disease after transplantation for other neurologic autoimmune disease.

    • Anonymous
      November 15, 2008 at 11:02 pm

      see disclaimer at the top of the thread.

      [B]Time for therapies to work[/B]
      There was discussion about how long it took therapies to work. IV IgG and PE were fastest. Steroids pretty fast but not as fast as those. Cyclosporin and cyclophosfamide may work next fastest. Methotrexate, azathioprine, and mycophenolate seem to take a long time to work—possibly as long as 12-18 months. When deciding if a treatment is working, IV IgG or steroids should get at least a three month trial, but azathioprine may need a trial to determine effectiveness of as long as 18 months.

      [B]Determining if something works.[/B]
      There was discussion about these points.
      Definition and subgroups of CIDP
      Doses and duration of the trials as too small a dose or too short a trial can adversely effect results and make one think that a medication may not work when it potentially would at a higher dose or if given more time to work.
      Scales for assessing benefit. The current scales are not optimal.
      There was discussion that in myasthenia gravis, progress has been made once they started defining not only remission off medications but also pharmacological remission (remission due to the use of drugs).

      [B]Long term outcomes.[/B]
      In a paper from 2006 JNNP with author Kuwasera or something like that, 38 patients with CIDP who had been treated with any therapy was looked at back in time to see how many improved. About ¼ were said to have a complete response, 60% a partial response, and the remaining 10-15% got worse despite any treatment given. The percentage of people responding to any of the big 3 is about 60-80% and none have been statistically proven to be better than the other in the CIDP population.

      [B]Features that affect Chances of not doing as well[/B]
      Axonal damage
      Muscle atrophy
      Delay to start treatment for more than a year

      [B]Socioeconomic Impact[/B]
      There was discussion of the huge impact that this illness has socioeconimically. About 40% of the patients in the outcomes survey had been on prolonged disability and about a 30% still were. More than half had to stop working for on average 5 years. There were on average long hospitalizations. IV IgG is very expensive. The illness and treatments for it have a high medical cost, but there is also a huge societal cost in lost work. Because the latter is so much greater than the former and because the impact on individual patients is so great, more studies of treatment need to be done even though this is a rare disease. .

      Many thanks to the many neurologists that so kindly provided information and answered questions at these talks including Drs Lewis, Hughes, Barohn, Koshi, Lisak, and Parry and the others no less important. This is an awesome group of neurologists and they deserve to be honored for their committment to these rare disorders.

    • Anonymous
      November 16, 2008 at 7:08 am

      With Hope,

      This is really amazing. the detail that you have captured is very accurate to what I heard. I appreciate being able to relive these by reading them. I did not take hard notes because my learning skill is to pay attention rather than writing and then I miss alot and get mixed up. Thank you very much for this.
      Amazing notations.

    • Anonymous
      November 16, 2008 at 12:45 pm

      For such Good clear summaries!
      Wish I could have travelled to such an affair, but even short trips around the neighborhood seem a trial at times.
      Your notes have confirmed what my readings have indicated over the ages [so it seems] – That diagnosis procedures [by many, many neuros] must catch up with current standards and that the full-nerve biopsy isn’t essential to many diagnoses, and that many test negative …at first, but later can test positive.
      It’s also good to know that treatments other than IVIG or PP can and do work for some folks… That is encouraging that neuros are thinking outside the box for alternatives. Alternatives are a comfort for all in the long run in that it’s not This or Nothing.
      Again I cannot thank you enough for such good information! It is very rich even in summary.

    • November 16, 2008 at 11:40 pm

      With Hope,
      As noted to a certain Dr. at the symposium, you are an incredible human being. Your wisdom, compassion, dedication and concern for others and their ability to have solid information to make decisions is truly amazing. Thank you! Anyone needing info in the future will be instantly informed because of you. The impact you will have on so many is unbelievable. Thank you from the bottom of my heart!
      Dawn Kevies mom

    • Anonymous
      November 17, 2008 at 12:53 am

      Thanks so much With Hope. Your notes are excellent. I have just copied them and saved them. Very helpful information. What a stellar job and it is much appreciated. You have indeed gone the extra mile. I’d give you a big hug if you were here .

    • Anonymous
      November 17, 2008 at 3:38 pm

      I agree with Tim and everyone else. Your notes are excellent ! Even tho I was there, I did not take that good of notes. Not like this, for sure !

      Once again,
      thank you so much…you are going to help so many.


    • Anonymous
      November 17, 2008 at 8:48 pm

      Thank you so much for this info! I am going to copy your notes as well to read again! Gabrielle

    • Anonymous
      November 17, 2008 at 9:02 pm

      Thank you as well. I have copied your excellent notes for my file and to show to my physician.

    • Anonymous
      November 17, 2008 at 11:47 pm

      Thank-you Hope for sharing this. Very interesting! 😀

    • December 7, 2008 at 10:12 am

      These are the notes I was refering to.

    • Anonymous
      December 13, 2008 at 4:30 am

      Thanks for this.