anti-amphiphysin antibodies, stiff-person syndrome, breast cancer‏

My wife was recently diagnosed with Auto antibodies to a 128-kd Synaptic Protein. According to The New England Journal of Medicine there are only Three Women with the Stiff-Man Syndrome and Breast Cancer. My wife also lost her hearing and has profound hearing loss in both ears. She lacks balance both her feet/ankles turn in and she needs to use AFO splints on both legs. She had serve muscle spasms in her right arm and was on 90 MG of diazepam. She was recently hospitalized for six months and is currently home. The fourth chemotherapy treatment removed the pain in her right arm. She is currently on Bacolfen, diazepam, tamoxifen, effexor XR and IVIG's. Our doctor evaluates her every three months and increased her bacofen and IVIG treatments. My wife is 46 years old and is becoming more and more frustrated with this disease and has a lot of questions:

1. Will here hearing come back?

2. Will the stiffness in her body go away?

3. Will she regain her reflexes, balance?

4. Will she need IVIG treatments for the rest of her life?

She goes to PT/OT twice a week which helps but she really wants to go back to work. If anyone has the time and can share their experience, strength and hope. I can be reached at: rtbucci@hotmail.com

Edited July 21, 2008 at 8:26 am

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Dear RT,

We are very sorry to hear about the awful ordeal that your wife has been going through.

Stiff person syndrome is considered an autoimmune disorder that can occur with or without a malignancy. From what you've written, it sounds like your wife has the form of stiff person syndrome that is associated specifically with a breast malignancy. The broader name for her disorder would be Paraneoplastic Neurological Syndrome (PNS).

PNS, which is rare, occurs when a malignant tumor is present. The body tries to fight the tumor by mounting an immune response (i.e. producing specific auto-antibodies ). That immune response causes the very miserable symptoms of PNS.

The typical scenario is that unusual neurological symptoms occur and a medical work-up is done. Sometimes, during the course of the work-up, a malignancy is discovered, and then it becomes apparent that the neurological symptoms are likely caused by PNS. However, sometimes the tumor is still so miniscule that it is not easily found.

Often, the PNS is diagnosed first, which then leads to the discovery of an occult (hidden) malignancy that needs treatment.

The auto-antibody that has been found in your wife is specifically associated with the presence of an active breast malignancy.

The mainstay of treating PNS-associated stiff person syndrome (or any other manifestations of PNS) is to (1) eradicate the tumor itself (surgery, chemotherapy, etc) and (2) to treat the terrible symptoms. It sounds like this is what is being done for your wife.

While we can't answer your specific questions, we can advise that treating the tumor (eradicating it) can often lead to marked improvement, and sometimes complete resolution, of the PNS.

NORD has a report on Paraneoplastic Neurologic Syndrome which we can provide to you. It gives an in-depth overview of the condition. If you'd like to have a copy sent to you, please either call us directly (1-800-411-1222, my extension is 246) or email me at rn@rarediseases.org.

In the meantime, the physician who wrote our PNS report, and who NORD feels is The Expert in the USA on paraneoplastic neurologic syndromes, is
Dr. Josep Dalmau (MD/PhD). He is Director of the Laboratory of Neuro-oncology and Paraneoplastic Disorders at the University of Pennsylvania School of Medicine. Dr. Dalmau can be reached at 215-746-4707 if you would like to contact him about your wife.

We hope that your wife's condition begins to dramatically improve with treatment of her breast tumor. Please don't hesitate to contact us if you think that we can help.

Sincerely,

Stefanie Putkowski, RN

NORD
Stefanie Putk

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Hi so very sorry to here of your wife's predicament. I have been fighting some of the very same symptoms as your wife for the past 14 years and because this is such very rare disorder nobody in this country seems to know any thing about it. So until know they have just pass it off as psychological disorder, but all the time I was on Diazepam until I made a complaint and then I was put on 20mg of Baclofen which made a difference, then finally I am know seeing a Neurologist, and he started to asked the right questions, and he increase the Baclofen and again it made a difference to the spasms then he mention This Person Syndrome, which I have being researching for some time. But it sound like your wife is in stage three of this illness and unfortunately the pain, the locking of the hands, and turning of the feet will only get worst as time goes on and their is no cure according to what I have learned about this illness. But because it sounds like this illness is more common in America than in the UK, where I live they may come up with something that may prolong it for a while, which I hope will then benefit me and the few others that I know who is suffering with this cocktail of illness, this is my name for this illness because their is no logic to it and out side the norm of normal nuerology. So I do hope you can find some comfort in this scripture Isaiah 33:24 Jehovah promises that in the not too distance future, "No resident will say that I am sick." This has kept me going for the past 14 years, and I hope that it will be of some help to you.

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Stefanie,

As I mentioned, my wife suffers from Paraneoplastic Stiff-Person Syndrome associated with breast cancer, anti-amphiphysin antibodies and serve hearing loss in both ears. She also has stage II diabetes.

I am trying to find another person with this exact variant as my wife's. Do you have any additional information, please let me know. I know there are a variety of other PNS disorders associated with anti-amphiphysin. I found only one publication in the New England Journal of Medicine (1993) that refers to only 3 known cases of this variant. http://content.nejm.org/cgi/content/full/328/8/546

I am trying to locate one of these women from this article or others if known.

Sincerely,

Robert

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Dear Robert,

It may be somewhat difficult to get in contact with other patients who have your wife's disorder because of the confidentiality laws that physicians must uphold.

However, I strongly suggest that you contact Dr. Josep Dalmau, Professor of Neurology at the University of Pennsylvania. His research is entirely devoted to paraneoplastic neurologic syndromes, and undoubtedly, he has a registry of patients with your wife's condition. There may be a way for his office to help you network with others who have the same condition. Dr. Dalmau's staff is very considerate and kind--I have spoken with them in the past and they will, at the least, be sympathetic to your wish to contact others who have gone through what your wife is going through.

(While your wife's condition is definitely rare, I can advise that there are definitely more than the three affected patients you mentioned reading about in the 1993 article. One study from Johns Hopkins mentions finding 10 patients (all women with breast cancer) who have the specific antibody that your wife has. That article was published in 2008.)

Dr. Dalmau's office can be reached at 1-800-7366. Here is a link to his hospital web page--
http://pennhealth.com/WagForm/MainPage.aspx?config=provider&P=PP&ID=9023

I wish you the best of luck and hope that this is helpful to you.

Sincerely,
Stefanie Putkowski, RN
NORD

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Stefanie,

Thanks for your prompt reply. According to Dr. Josep Dalmau and others. Dr. Jerome Posner at Memorial Sloan Kettering Cancer Center in New York. Is the leading expert in the world regarding Paraneoplastic Neurological Syndromes. Dr. Jerome Posner is also my wife's doctor. I haven't asked him this question. I am trying to research how rare the variant of her condition really is. As far as my research on her illness, there is no other documented case associated with hearing loss and she is the 4th documented case.

It is hard for her to imagine, just how rare her condition is. My wife and I are grateful to all the doctors who have dedicated their lives to this field of study. I know due to confidentiality laws it is difficult to obtain certain information. I can't thank you and N.O.R.D for the excellent work on these kinds of issues. I thought it both beneficial to share my wife’s story with others.

Sincerely,

Robert

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Robert,

Thank you for advising us about Dr. Jerome Posner. We will enter him into our researcher database.

I don't know if this will help you in your search for statistics for the variant of your wife's condition--but it is worth trying if you haven't already done so. There is an international consortium of paraneoplastic researchers called PNSEURONET -- http://www.pnseuronet.org/. Perhaps you can find some guidance and information there.

And we agree with you completely--it is beneficial to share your wife's story with others. It might eventually lead to some answers for you, and will also serve to educate others.

Thank you very much for your kind words about NORD.

Sincerely,
Stefanie Putkowski, RN
NORD

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Thanks for the additional information. Anti-amphiphysin antibodies is now and forever linked in your search database. As information and treatments be come available patients and caregivers are empowered to help ourselves and others.

Best regards,

Robert

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Stefanie,

I came across this publication with Stiff-person syndrome with amphiphysin antibodies Distinctive features of a rare disease by Beth B. Murinson, MS, MD, PhD and Joseph B. Guarnaccia, MD. If this is the study you are referring to, please let me know. However, all except one had breast cancer; none had diabetes. I am aware through my research there different types of cancers being associate with amphiphysin antibodies. The question my wife wants to know is how many Paraneoplastic Stiff-Person Syndrome associated with breast cancer, anti-amphiphysin antibodies, serve hearing loss and diabetes have been documented or reported?

I am hopeful there are others out there willing to sharing the experience, strength and hope with us.

Robert

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Hi Robert,

Yes, I believe that we are referring to the same study by Drs. Murinson and Guarnaccia at Johns Hopkins.

I have not been able to find any documentation of paraneoplastic stiff-person syndrome with the anti-amphiphysin antibody, that is also accompanied by diabetes and hearing loss like in your wife's situation. What I did find interesting is that in the study abstract that we're talking about, it does say, "...none had diabetes." That notation sort of comes out of the blue, so there must be some correlation.

It may be helpful for you to read the entire study. The journal that it's published in is "Neurology," Dec. 9, 2008. Your local hospital may have this journal in their library.

Dr. Murinson is well-known in the field of stiff-person syndrome. It might be worth your while to send her an email with your question. Her email is provided in the study-- bb@jhmi.edu.

Best of luck!

Stefanie Putkowski, RN
NORD

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Stefanie,

Thanks for your prompt reply. As you know there are several variants of Stiff-Person Syndrome. In my wife's case her EMG was normal and she was negative for GAD 65 antibodies. The early onset of her condition mimic CIDP. We went to see Dr. Norman Latov, the leading expert on CIDP to confirm this diagnosis. He stated the medical evidence does not support a diagnosis of CIDP. He ordered another EMG. It was only after her 3rd EMG did something finally showed up. Along with MRI of the chest which revealed a mass in her left breast. And blood work for Paraneoplastic serum test completed at the Mayo Clinic did we have a confirmed diagnosis of Paraneoplastic Stiff-Person Syndrome. While in the hospital my wife had serve muscle spasms in her right arm and was on 90 MG’s a day of Diazepam. The doctors at the hospital tried Plasmapheresis along with Baclofen. Neither of these treatments seem to work at the time. It was only after her 4th Chemo of cytoxin did the serve spasms in a right arm improved and over time she was able to reduce her diazepam from 90MG’s a day to 2MG’s at bedtime. It is my belief Stiff-Person Syndrome associated with confirmed antibodies lend it self to an autoimmune disease. How other forms of Stiff-Person Syndrome without an antibody variant are classified, I do not know. It is my understanding the Medical community has a wide range of views on this very subject. As you know, Stiff-Person Syndrome is a very complex disease.

In my wife’s case. I believe if the doctors can find a treatment that stops anti-amphiphysin antibodies from producing; my wife’s symptoms would greatly improve over time. In Paraneoplasitc Neurological Syndromes, treating the tumor is paramount. However, there may still be occult cancers and antibodies continuing to attack the body.

My question is: Does any of the therapies such as IVIG’s, Plasmapheresis or Rituxan target anti-amphiphysin antibodies by reducing or eliminating them? I know these are not specific treatments for anti-amphiphysin antibodies. Has anyone fully recovered or greatly improved and still tested positive for amphiphysin antibodies?

I am not a doctor, I am a loving husband who has advocated on my wife’s behalf and will not rest until she’s well. It is difficult for me to gain access to non-treating doctors to have some of these questions answered. If I was an investigator reporter it would be much easier to obtain this information. Doctors are interviewed all the time and provide their medical opinions. I’ve tried several times of the past two years to get additional information from Dr. Murinson. I am not asking for any non-treating physician to comment on my wife’s medical condition. I am only looking for information on this variant of this disease. “Out of the darkness into the light”, Right?

Thank you so much for your generosity of heart and for your kindness.

Sincerely,

Robert

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Hi Robert,

It seems your wife has a rare form of a rare disorder, paraneoplastic SPS. I am sorry for what you both are dealing with.

I have the 'classic' variant of SPS - the insulin-dependent, GAD+ combo. After living with SPS for approx. 20 years, diagnosed 15 years ago, I wonder if I will be on IVIg for the rest of my life, if I will improve or worsen. Everyone with a chronic condition has unanswered concerns without guarantees, but...

Medication and IVIg have alleviated the severity of my symptoms. I continue to learn to live a very full life within my diagnosis. ;)

In communicating with many individuals with SPS or other autoimmune diseases, many of us have several autoimmune nasties in a gang assault on our health. Customized diagnostic specialties?!!!

Just my stiff perspective, I am not a medical pro. ;) Ask your neurologist to check if your wife has an autoimmune hearing problem or some other cause for hearing loss. Often, we [patients & physicians alike] want to connect all physical dots to SPS when it may be a separate diagnostic issue.

Many individuals [SPS or not] have type-ll diabetes. Your wife's diabetes may also be a separate issue from her paraneoplastic SPS. It is usually insulin-dependent, or type-l diabetes that is associated with Stiff Person Syndrome with the GAD autoantibody, from my understanding.

A good link for web search:

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=184850

There is a section on paraneoplastic SPS. The reference numbers and light bulbs will link you to good abstracts. If you find an article of particular interest to you, contact someone you know who has access to an online medical library to get a printout of the entire article.

From what I have read about paraneoplastic neurological syndromes, prognosis depends on the type of cancer, effective cancer treatment, and neurological deterioration responsive to treatment.

I am aware of one hopeful outcome. I met an amazing nurse with a complex variant of SPS, resistant to treatment. This retired nurse communicates with a parent of an individual who had paraneoplastic SPS with Hodgkins. When the Hodgkins went into remission after chemo, so did the SPS.

Robert, your concern, dedication, and interest have been a great encouragement to me. I hope the future has some positive resolutions for your wife's health. May God bless you both.

Stephanie, I greatly appreciate the time and effort you made to respond compassionately and professionally to Robert's questions. I learned a lot from this discussion thread.

"The purpose of life is a life of purpose."

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Betty,

Thank you for your kind words. I've seen this article and many like it. My wife’s hearing loss is rare and no one can explain it. I've researched my wife's hearing loss far and wide and found Dr. Jeffrey Harris in San Diego who specializes in autoimmune hearing loss. He is perhaps the best qualified to explain it and he can not.

I am hoping based on want I've read and learned the answers and treatments are out there. The key is patients and perseverance. Will my wife’s case provide the answers the doctors have been looking for or will the doctors find the answers my wife and I am looking for?

There are occult cancers typically associated with Parneoplastic disorders and perhaps prescribed treatments succeed or fail upon whether or not they still exist. My wife is currently on Rituxan. I’ve requested her antibody levels be checked before and after each treatment. I suspect until we find a way or treatment to stop her body from making this antibody, her neurological symptoms won’t improve. What’s next Cytoxan or Plasmapheresis?

Robert

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Greetings again Robert
Betty has certainly taken all my words to you.
It surely must be hard going for you both. I am certain you both will keep the pressure on this bizarre syndrome.
Regarding the Rituxan, I think we have discussed this before, however, can you let me know how things
go with this medication
I will be starting maintenance doses in the next couple of weeks.

KInd Regards to you and your wife.
Rick
Sydney Australia

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Hi. My name is Chrysta and I am 18 years old. Just recently my blood test came back positive for Amphiphysin. I am currently consulting with an Oncologist.

But what I wanted to know is what is the likely-hood of having this antibody and NOT having cancer? Are there cases of someone having this antibody and not having cancer? And I don't have any symtoms of Stiff-Man Syndrome, so what are the cases of people having this antibody and not having SMS or Nuerological symptoms?

I had a PET scan and it came out clean, although my Oncologist said that doesn't mean that I don't have cancer. She said that the two cancers mainly associated with Amphiphysin, Small Cell Lung Cancer and Breast Cancer, are likely not to show up on a PET scan.

Also, my sister had Ovarian Germ Cell Cancer when she was 16.

Sometime next week I am going back to my Oncologist and she is going to have me tested for more specific tumor markers and of course retested for the Amphiphysin. Also, if cancer in the breasts is not easily found on a PET scan and not easily found on a mammogram (for someone my age) how would it be found? Same with the lung cancer? If it can't be found on a PET scan, how do we find it?

It's frustrating to sit here knowing that I could possibly have cancer, especially since almost every site I have been on, on the internet shows just how highly related cancer is.

Plus on top of this health issue, I have others that I can not seem to get better. I have PolyCystic Ovarian Syndrome, Hashimotos Thyroiditis, and Insulin Resistance. I have severe fatigue, I sleep constantly and I can't stay up for very long. I have severe night sweats and weight issues. I also had high ACTH when I had that tested. I also have had Social Anxiety for six years now, and I have plateaued with that. I am going from doctor to doctor trying to get better. It's so frustrating to be so young and have so many health problems already setting my back. I feel hopeless most of the time, and now I could have cancer too.

Thanks for any help. :)

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Also, I consulted a doctor online, on allexperts.com and he said that I probably don't have cancer just because I have this antibody and because I don't show more Paraneoplastic symptoms.

But what I don't understand, is if I don't have cancer, and I don't have a PNS, then why do I have this antibody? I can't have this in my body for no reason. It either comes from a PNS or cancer, it can't be there for nothing.

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Hi Chrysta,

Unfortunately there are occult cancers associated with Paraneoplastic Neurological Syndromes, such as Amphiphysin antibodies.

I can be reached directly via email @ rtbucci@hotmail.com

I can send you some additional information and helpful links.

Please understand these conditions are rare and are both difficult to diagnose and treat. There is a lot of help out there. I am not a doctor, so I can't answer medical questions; however I am more than happy to share additional information with you.

The most important thing is to stay positive and hold on to hope.

Robert

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Chrysta this is for you.
I was diagnost with Breast Cancer at 27 and because of my young age they said it is hard to detect even with a mamogram, so my Dr. ordered an MRI to get a better look, and that test showed the most information. May be you should ask for one to ease your mind, to confirm or rule out Breast Cancer. Because I was so insistant that the lump I felt was not from an injury I caught the tumor at Stage 1. I am waiting on test results for Stiff Person Syndrome now. I saw a show that talked about it and the symptoms sounded just like me. When I read online that there is a Breast Cancer variant I thought, This would connect all the dots. But SPS is so rare I am preparing myself to continue the search for my pain and stiffness.
I guess I am kinda going through the opposite route from you. I hope you are cancer free, but if not, you have someone to talk to. Good Luck.
BCsurvivor

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Hi BCsurvivor.

I am sorry that you had to go through that, but luckily you found it early.

I recently had a breast MRI and it came out clean. So, now since every test I had came clean I am going to get annual testing to make sure it stays that way.


Thanks for the concern,
Chrysta

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Hi Chrysta, I'm from B.C. too, I have Stiff person syndrome, and the more I go on different sites the more I am finding out that this is becoming not so rare. I'm sorry your going through this. I have been researching and trying to figure out what causes it, so far found out that PCP's attach them selves to the 2nd and 3rd atom which is found in chlorine and we drink the water that is chlorinated, I also know that I can't have the IVIgG Plas. as there is not enough of it here. So I take Valium which does help , it replaces the enzyme that is missing neurologicly, this is what it was actually intented for. Any way I hope you get your results soon. I'm thinking of leaving B.C. as from what I hear we have the worst Health care in the entire province. I kind of believe it, I couldn't get a pap smear or a mamogram here. So I'm going to the coast in Aug. and then to Sask in July and the again in the fall, I want to see the difference in health care quality. I hope you are being treated well, take care
Ingrid/Cranbrook, B.C.

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