not really new but still desperately in need of help

Hi all.

I have already posted here some time ago; http://www.gbs-cidp.org/topic/new-here-plz-comment-cidp-mngie/

Meanwhile, I have tried to figure out what the cause of my neurological problems. I still have no clear answers, though I feel I may be somewhat nearer to the answers. I say answers as I do believe that there is no single answer for my problems.
Please go to my last post by the link above for reading my background story. In a nutshell: I have a long medical history, got diagnosed with chronic intestinal pseudo obstruction at age 22, have had multiple surgeries, have an ileostomy and a bladder catheter etc etc… It would take too long to explain my background in detail.
January 2010, I experiences what I think was the onset of my neuropathy (or better one of my neuropathies, more to come later); I had needles and pins pain(shooting pain in my feet, it was not too bad not bothered me especially as I have already quite a bit pain from my underlying condition. At that point, I was heavily treated with both oral and iv antibiotics due to chronic UTI and recurrent septicemia of the iv line I needed for parenteral nutrition.
However, in retrospective, I really cannot say if the neuropathy was there before but had remained subclinical before it was triggered by the antibiotics.
In any case, I do remember that even before, I had experienced some kind of weakness in the upper arms and legs which made holding something above the head exhausting. I had also noticed that I couldn’t stand up from a squatting position any more.
When I began to experience the shooting pain and pins and needles (without any other paresthesia) in the feet we thought that it was drug induced by the antibiotics. Unfortunately, we couldn’t do much about it as I needed them. However, we switched to antibiotics that are less or not really known for causing neuropathy and I began to have vitamin b12 shots. Under this regime, my pain improved (though I regularly took oral antibiotics).
When the bladder infections got really bad and I had to up the dose of the antibiotics I noticed a pretty immediate worsening of the neuropathy pain. And this reaction was totally independent of the kind of antibiotic I took (including some a. which are not known at all for causing neuropathy)

In summer 2010 I began IvIG therapy as we hoped to boost up my immune system and to limit the recurrent septicemia. Unfortunately, I had severe side effects, including inflammation of the small vessels and aseptic meningitis with the latter lasting almost 8 weeks.
We stopped the IvIG therapy after only three sessions. Ever since then I have been experiencing reactions to almost any drugs I had to take which unfortunately always causes a pretty acute worsening of y neuropathy. These reactions should increase in frequency and severity within the last year leaving me now impossible to take the drugs I’d need. I actually believed the IvIG therapy made my neuropathy worse or triggered the process that had been lurking to show up.

In the beginning of 2011, I decided to try to wean off all drugs/antibiotics to give my immune system and peripheral nerves a rest. The discontinue was not without risks as I still have chronic infections but eventually, I succeeded. In the following two-three weeks, I began to experience dramatic improvement of my neuropathy by taking active vitamin b12/methylcobalamin. After three weeks the pain had disappeared.
Then, I experienced something what I thought was a bug but I remember that I didn’t have typical symptoms of a bug. I did feel sickly but what actually striked me was the intermittent feeling of heaviness I experienced in my limbs. Fortunately after two weeks all my symptoms had gone. But then, I began to have what I consider as pains from impaired circulation; they were throbbing and they were totally different from the nerve pain I had experienced before.
In the beginning they were just annoying but after one week, they increased in severity and after three weeks I could barely stand the pain any more. I began to notice swelling veins in my feet and hands and the pain now expanded from the feet to the hands including all four distal limbs.
During that time, I also had blood drawn and although my veins had never been in a good shape this became nearly impossible due to severe vasospasms. (note: I have always had some kind of vasospasms and impaired circulation probably due to some autonomic dysfunction associated with my CIPO)
After 4 weeks, the nerve pains returned and from then on, increased in severity. I also noticed some kind of strange blisters on my fingertip and toes which were extremely painful and itchy, and after some time, the areas on my toes became numb. From then on, I knew something was really really wrong and that this wasn’t the neuropathy I had dealt with the year before (especially as I had had dramatic remission from it before).
I begged for help but nobody knew what to do and since I am a complex and difficult case anyway they obviously decided to just wait and see. The docs just put aside that I knew that this was something new and different and that it would have severe consequences if left untreated. Finally, my Gi doc who knows me well agreed to give it a trial and prescribed prednisone. Prednisone actually decreased the throbbing pain and made the blisters disappear. However, it made the actual nerve pain worse and I once again noticed that I had an immediate worsening after taking the drug. I was totally confused.
However when I tried to wean off the cortisone the throbbing pain reappeared. Within two months I continuously struggled between lowering the dose of prednisone and somewhat decreasing nerve pain AND upping the dose but increasing nerve pain. Finally, I made a cut though I still experienced the throbbing pain on and off (though not as bad as before). I noticed that creamed that promoted blood circulation also helped somewhat with the pain. Eventually, 6 months after the acute onset of the pain I began to notice that the pain had finally subsided. However, though I had been off all drugs since the prednisone withdrawal my nerve had been steadily deteriorating and spreading further.
At this point I have severe pain in my feet (severe burning pain, with episodes of shooting/pins and needles pain) and all kinds of paresthesia you can imagine (feeling like walking on sand, tingling, pain/dysthesia from touching etc etc). I also have moderate-severe pain in my hands. Oddly, the middle parts of my limbs seem to be pretty spared: the most distal and the most proximal ends of the limbs are most affected (the most distal being the worst). When I am very bad, I also have shooting pains in my shoulders and head, sometimes radiating into my face. I also experience some muscle twitching but that is not on daily basis.
The first neurological consultation was totally useless. Now, I have been in patient in a rheumatological unit where I was sent to the neurologist again and I gained some hard data on my neuropathy from NCS and autonomic testing.
During the whole year I had been consultating numerous docs including rheumatologists which ruled out an autoimmune disease; all my antibodies and rheumatological markers were fine. Nobody knew what was wrong. Druing my in patient stay at the neurological unit which turned out useless I had a PET/CT done. This was the only good thing they did there; unfortunately, they didn’t make anything out of the finding. I got into touch with the radiologist and to make a long story short: he recommended following up the enlarged thymic gland due to the possibility of a tumor and my symptoms being a paranopleastic syndrome. In December 2011 I finally had a chest MRi in one of the top cancer research facilities and the radiologist there confirmed that the thymic gland was indeed too large and that the clinical picture and some of the radiological findings could indicate a paraneoplastic syndrome secondary to a mediastinal tumor. Unfortunately, the radiological findings are not definitive – neither for “only a benign enlarged gland” nor y thmic tumor although there is s slightly increased tendency towards the tumor. In any case, to be sure one has to do surgery and examine the tissue. Now, I am looking for a good surgeon as my case is very complex.
Back to the recent hospital stay at the rheumatological unit: They excluded once again a definite autoimmune disease like lupus or scleroderma and look for various autoimmune markers but everything came back normal. They then sent me to the neurologist and obviously they were much more sophisticated than the neurologist at the former clinic. As I haven’t had a NCS before (well I had one at the other clinic but it was useless due to manipulation) they were just asked to conform the neuropathy by objective means. I didn’t ask them for the possibility of a paraneopasltic neuropathy; I wanted to wait for the test result and their proposals. Moreover, I didn’t pointed out quite well that I think that there are two different processed causing the overall somewhat confusing clinical picture of my neuropathy They did a NCS and autonomic testing and both tests showed some abnormalities: I do not have the report yet, but I already know that the NCS showed slowed nerve conduction study (I think it may be only in the sensory nerves but I am not sure) indicating an ongoing demyelinating neuropathy. The autonomic testing revealed severe autonomic and small fiber neuropathy.

…They said that they would like to test for Fabry due to the severe small fiber involvement and for monoclonal gammopathy as well. Also, a lumbar puncture is planned because they want to exclude the possibility of CIDP (though the clinical picture does not fit that well for CIDP: I predominantly have sensory and no obvious motor symptoms). But I am the one who knows best that humans as well as conditions don’t always follow the textbook descriptions. All in all, they want t to start a comprehensive search for a possible underlying cause next time.
I am going to be in patient for a full work up sometime in the upcoming weeks. In the meantime, I have thought over the findings and my symptoms and the course the condition took over and over again. I am pretty smart and used to research by my own, this is how I got my diagnosis CIPO: when you have rare diseases much is up to you.
I do think that I CIDP is a possibility but I am not really convinced at the moment that I do have it. I am now even more convinced that there are two different kinds if neuropathies in my case. I think the ongoing demyelinating neuropathy of unknown origin is the neuropathy that started already two years ago (or at least became symptomatic the might had been subclinical before); this would explain the dramatic improvement under methylcobalamin. The drug intolerances and strange reaction/worsening of the neuropathic pain to drugs (when I had never had problems with drugs allergies and intolerances before) could be attributed to a diffuse, unspecified autoimmune process, as part of the paraneoplastic syndrome due to the possible tumor. A paraneoplastic sensory neuropathy would well fit the clinical picture of what I have been experiencing since spring 2011: All in all, there is the
1. Acute onset of what I now consider as acute autonomic neuropathy with subsequent occurrence of small fiber nerve damage and neuropathy
2. The sensory predominance and
3. The absence of autoimmune markers which is nothing uncommon in paraneopalstic syndromes while obviously there is something immunological going on
4. The rapid progression and involvement of unusual sites for a usual neuropathy and I think even CIDP
5. 6 weeks ago: acute onset of what is very likely erythromelalgia, a vasomotor condition which causes swelling, redness and increased temperature and severe burning pain of the feet due to involvement of the small nerve fibers; erythromelalgia is sometimes associated with tumors thus being another paraneoplastic syndrome and is caused by dysregulation of the vessel tone due to autonomic dysfunction
6. development of what probably is autonomic neuropathy of the heart with QT prolongation
7. I haven’t found any info about the possibility of the occurrence of a demyelinating (sensory?) large fiber neuropathy and a small fiber neuropathy which is by definition an axonal neuropathy at the same time. Many neuropathies do involve both large and small fibers but these seem to be axonal neuropathies as the same process damages the axons of the large and small fibers.
8. I have slightly elevated NSE and markedly elevated LDH which can be seen as tumor markers in the absence of a benign disease that would explain the elevated levels

So why do I want an opinion of you at all?
1. Because I don’t want to exclude the possibility of CIDP unless the tests have been negative.
2. There is much knowledge and smart people here who are used to research by their own like me.
3. You may know more about the differential diagnosis of demyelinating neuropathies other than CIDP as you don’t find much info on that in the internet – if you have read my old post you know that I’d like to be tested for MNGIE as this could be another differential diagnosis – what do you think?
4. You may know if a demyelinating neuropathy can be indeed associated with a severe axonal small fiber neuropathy that is unusual in distribution and may rather be a small fiber ganglionopathy/neuronopathy ? Do you agree that there is at least the possibility of two different neuropathies in my case?

Sorry for the length of my post but my case is just so complex and writing down helped me to get things in sorted out in my head that is spinning around. BTW, my neurological work up for actual CNS diseases like MS etc have been always normal, also MG was easily ruled out. I would be so glad if you could help me somewhat along…..
I am in so much pain each day and sometimes I can’t hold back the tears and I am certainly nobody who readily cries. I have been used to pain since childhood. But this is just too much especially as I have chronic bowel and bladder pain from CIPO as well, and I cannot take the drugs I’d need for my CIPO or for adequate pain management due to the severe drug intolerances