Diagnosed with stiff man syndrome?
 

Due to my full body muscle dystrophy, my neuro doc has done extensive bloodwork. The only thing to come back abnormal was ga65 which is an indicator for stiff man (I am stiff but not sure if this is correct) so the tx he wants to do is an iv of retuxemb..we already tried ivig. Just not sure what to do...


Thoughts?

Debbie

The best thing you can do is go with the proposed treatment. There isn't a cure for Stiff Person Syndrome or the variant Stiff Limb Syndrome and there is no clarity about the cause. It looks as though they may have multiple causes. The treatment they have suggested has shown some good results for long term symptom control/management. So have long term, large doses of muscle relaxants ,IVIG which you have had and some of the usual drugs like gabapentin and anti anxiety drugs. Specialist physio can make a massive difference to some people. To some extent it depends which stage of the disease you are in. Ultimately everything they do is about slowing progression to try and minimise the severity of the symptoms as long as possible. For many people the drugs give them good long term symptom control and halt any progression for a long time.

My neurologist believed I had SPS but then changed his mind. Oddly enough, I have an acquaintance who was diagnosed with it at the same time as I was told they didn't think I had it. It's a crappy diagnosis to get but if its what you have then at least you know and can start to move forward.

Good luck with the treatment.

Ty
 

Thanks for your response. Guess I am. Unsure about the diagnosis, my biggest problem is muscle atrophy, but my back and neck r very stiff, at
This point. I have to try something to stay in the game..my body is wasting away ..I truly believe it is all just spread of the rsd (atypical)

Deb

Debbie

Why are you so doubtful about the diagnosis of SPS? Is is because you don't want to have yet another crappy diagnosis? Is it that you don't think much of the doctor who diagnosed you? Is it perhaps fear? Is it that you don't think you meet the profile for SPS?

Any of these would be more than understandable. I just wonder why you are not inclined to believe them in this new diagnosis. How sure have they said that they are about the diagnosis? Could you perhaps ask them to sit with you and explain slowly why they have come to the diagnosis and exactly how sure they are. If you thing they are just lost and this is clutching at straws then I could see why you are reluctant to take more treatments.

There is some decent information out there on the web about SPS although its very rare and poorly understood so you can imagine what that means! If there is anything else I can do to help then please just ask me. I had a clueless neurologist so I always am concerned that my SPS rule-out could have been incorrect. I share a lot of the SPS symptoms hence why they suspected it but they weren't able to do a lumbar puncture due to my movement problems so that meant they could never do all of the necessary tests.

TY
 

the only reason he said stiff man is because of an elevated GAD 65 and of course some of my symptoms. I guess I am unclear if an elevated gad 65 definitely confirms stiff man because I had that in previous blood work and he said i may have stiff man....i hope it is sms as then there is a possible tx.

Thanks for your support

Debbie

It all seems a bit unclear as to whether there is certainty about the diagnosis or not. Maybe you could try and get them to establish once and for all how certain they are or whether there is anything else they think it could be.

I don't think I would be hoping it was SPS though - I know it feels good to have answers rather than having no clarity about what is wrong but SPS is a pretty nightmarish diagnosis and the treatment options are very limited. In the later stages, there is no effective treatment, care is palliative and it can progress to cause death. You just have to hope you don't progress and the symptom controlling medication is effective for you.

I'm not trying to be the merchant of doom, just honest. Having researched SPS because I was thought to have it, I know how bad it can be. They never confirmed what tests they did on me and the neurologist was clueless so there is a slim chance I could be living with it and not even know! I'm not into giving out sugar coated platitudes but I do sincerely hope that you get an improvement from the latest treatment they are offering. There is some decent info on the web about SPS and you might find it is helpful to do some reading so that you know what other potential medications could help.

Update
 

I just had blood work to r,o diabetis as the cause of my elevated gad65. If I don't have DM then I will feel more confident trying iv retuxenb

Ty
Deb

GAD65, cause or effect?
 

Dear Debbie -

Understand that concern about the GAD65 in your blood-work. But I necessarily jump to wouldn't jump to any conclusions over it, especially where to the best of my understanding, the only standard/generally-accepted treatments for Stiff Man/Person Syndrome (hereinafter SPS) are are essentially palliative therapies, and I've been on two of the biggies for years in an attempt to deal with the spasms associated with CRPS: (1) CNS-focused muscle relaxants, e.g., Balcofen, and (2) benzodiazepines such as Xanax.

And here's the deal, as recently as 2008, articles were being published to the effect that "Analysis by LIPS of 40 sera samples from SPS and control subjects for anti-GAD65 antibodies revealed dramatic titer differences allowing diagnosis of SPS with 100% sensitivity and 100% specificity." High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff-person syndrome, Burbelo PD, Groot S, Dalakas MC, Iadarola MJ, Biochem Biophys Res Commun. 2008 Feb 1;366(1):1-7.

But now we know that anti-GAD65 antibodies are found in a number of conditions, on account of which any claim of "100% specificity" of a diagnosis of SPS. See, e.g., GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA), Towns R, Pietropaolo M, Drugs Future. 2011 Nov;36(11):847 [I missed the reference to being tested for diabetes at the end of your last post - sorry]; AND GAD65 Positive Autoimmune Limbic Encephalitis: A Case Report and Review of Literature, Sharma A, Dubey D, Sawhney A, Janga K, J Clin Med Res. 2012 Dec;4(6):424-8.

Indeed, there has also been discussion is recent literature suggesting that earlier research may have inverted the causation altogether, on account of which increased levels of GAD65 may be the result and not the cause of neuro-ischemic pain and spasticity conditions in general. Compare,
Epigenetic suppression of GAD65 expression mediates persistent pain, Zhang Z, Cai YQ, Zou F, Bie B, Pan ZZ, Nature Medicine 2011 Oct 9;17(11):1448-55, with, Combinational spinal GAD65 gene delivery and systemic GABA-mimetic treatment for modulation of spasticity, Kakinohana O, Hefferan MP, Miyanohara A, Nejime T, Marsala S, Juhas S, Juhasova J, Motlik J, Kucharova K, Strnadel J, Platoshyn O, Lazar P, Galik J, Vinay L, Marsala M, PLoS One Epub 2012 Jan 23.

And, for a general statement of that proposition - which I would encourage you to share with your doctors, see, Calpain cleavage of brain glutamic acid decarboxylase 65 is pathological and impairs GABA neurotransmission, Buddhala C, Suarez M, Modi J, Prentice H, Ma Z, Tao R, Wu JY, PLoS One Epub 2012 Mar 12.

But lets make this easy. Check out the Wikipedia article on Stiff person syndrome . Here's what it list as the symptoms:

People with stiff person syndrome tends to present in 3 different stages: early, late and end stage. In the early stages, there are few objective findings indicating SPS during the initial assessment. SPS will begin insidiously in the axial muscles. Patients will present with an exaggerated upright posture and have stiffness and pain in the whole back. Sleep disturbances are also common due to muscle spasms waking them. In the late stages, proximal limb muscle become involved and the patient tends to move slower as fast movements will cause the severe spasms. Emotions such as anger have been shown to have a link to causing the spasms, which begin in this stage. Exaggerated lumbar lordosis becomes more evident in the patients. Depression can be comorbid with SPS at this stage due to the patient’s quality of life decreasing. In the end stage, activities of daily living such as eating and simple movements become hard to perform. Skeletal fractures and muscle ruptures occur quite often along with joint deformities. [Footnotes omitted.]

Funny, but I don't see a lot of references to disproportionate and/or burning pain, edema, discoloration, skin temperature changes across the body, etc.

Debbie - You and I have been on these forums for a long time. And I can pretend I recall every post you've put up along the way, but I have to think that a number of your complaints had nothing to do with SPS. IF AND ONLY IF that is the case, then I suspect it's probably more appropriate to consider your elevated levels of GAD65 as the EFFECT if your pain, spasm and rigidity, rather than the other way around.

I hope this is useful.

Mike

Ty
 

Hey mike,

Thanks for your input..here's the.

Ty
 

[QUOTE=debbiehub;950876]Hey mike,

Thanks for your input..here's the thing. I have full body muscle atrophy worsening each day. My legs r getting so thin and weak and arms r fatiguing quickly. So if I do have some autoimmune disease maybe the retuxemb iv will halt it,,,at the rate I'm going I have to try something....not sure what else I can do?

Ty
Deb

Did your doctor tell you about the FDA-mandated warnings on Rituxan?
 

Debbie -

I completely understand. I know rheumatologists who regularly prescribe Remicade (Infliximab) for CRPS and understand that Rituxan (Rituximab) is just one more step down the same path. Nevertheless, I choose not to try Remicade because of the possible side effects (lymphoma) where I already carry a precursor to multiple myeloma, and my "quality of life" even with CRPS was not so dire that I was willing to roll the dice. But from everything I've heard from you in the last few months, your situation is pretty miserable as is.

That said, may I ask if your MD has fully advised you of the current FDA-mandated "Black Box Warning" for Rituxan? I ask only because - at least as of the last time I checked - it beats that of Remicade by a fair piece:

Some people who received rituximab experienced severe reactions to the medication. Some of these people died within 24 hours after they received a dose of rituximab. Most of these deaths happened after the first dose of rituximab. Tell your doctor if you have or have ever had chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells), mantle cell lymphoma (a fast-growing cancer that begins in the cells of the immune system), an irregular heartbeat, or heart or lung disease. If you have any of these conditions, or if you are female, there is a greater chance that you will experience a serious reaction to rituximab. If you experience any of the following symptoms, tell your doctor or other health care provider immediately: hives; swelling of the lips, tongue, or throat; difficulty breathing or swallowing; dizziness; fainting; shortness of breath, wheezing; blurred vision; headache; pounding or irregular heartbeat; fast or weak pulse; loss of consciousness, fast breathing; pale or bluish skin; pain in the chest that may spread to other parts of the upper body; weakness; excessive tiredness; sweating; or anxiety.

When rituximab is used to treat non-Hodgkin's lymphoma (NHL; a type of cancer that begins in a type of white blood cells that normally fight infection) it may cause a condition called tumor lysis syndrome (TLS; a group of symptoms caused by the fast breakdown of cancer cells). TLS may cause kidney failure and the need for dialysis treatment. Tell your doctor if you are also receiving cisplatin (Platinol). If you notice that you need to urinate less often than usual or that you produce less urine than usual, tell your doctor immediately.

Rituximab has caused severe skin reactions. These reactions have caused death. If you experience any of the following symptoms, tell your doctor immediately: painful sores, ulcers, blisters, rash, or peeling skin.

Some people who received rituximab developed progressive multifocal leukoencephalopathy (PML; a rare infection of the brain that cannot be treated, prevented, or cured and that usually causes death or severe disability) during or after their treatment. If you experience any of the following symptoms, call your doctor immediately: difficulty thinking clearly or walking, loss of strength, vision problems, or any other unusual symptoms that develop suddenly.

Talk to your doctor about the risks of using rituximab. [Emphasis added and 'right on' re the last sentence.]

http://www.nlm.nih.gov/medlineplus/d...s/a607038.html

So, at a minimum, I would STRONGLY recommend that, before initiating treatment, you be "worked up" for (1) chronic lymphocytic leukemia, (2) mantle cell lymphoma, (3) irregular heartbeat (sinus rhythm) - a simple EKG should due the trick - AND (4) "other" heart or lung diseases. This should probably include a simultaneous/concurrent "CT angiogram" and a CT scan of your lungs - which would at least minimize your radiation exposure - along with an echo-cardiogram and a pulmonary function study of some sort, to rule out asthma, etc.; I assume with your recent blood-work they've already ran a metabolic panel as well, just to check on your current kidney function, for whatever good that may do.

I do not mean to be alarmist, but the Black Box Warning for Rituxan is as heavy as anything I've ever read. So if it sounds like I'm suggesting what could turn into a two-day battery of essentially non-stop testing, it's because I am.

Mike

Thanks for your input. Yes, they have me going for bloodwork. cardiologist, and chest x-ray. I think my neuro is pretty up to date on this drug. he is a well known MS Doc....Its going to take a while to get insurance or donation from the manufacturer because it is an off label use.

Debbie

Debbie -

Very happy to hear you're getting a good medical work-up before going on Rituxan.

Just curious. Has anyone explained to you how (or if) SPS is distinguish from dystonia? (The latter of which - even if relatively rare - is a still too frequent side-effect of CRPS?) From what I was reading last night, they both pretty much come out the same in the wash, including having strong GABA-genic components. Then too, neither appears to be associated with muscle wasting, whether or not due to appetite suppression, suggesting the operation of another player, such as cachexia, very possibly induced by the same underlying condition.

More later, running late for a school meeting.

Mike

PS Please see the corrections - in bold - to my earlier "GAD65, cause or effect?" post. I had been up all night and misread what was then your immediately preceding post. Txs.

Debbie

The questions FMichael is asking is why I was asking in my early posts about exactly why and how the doctors had arrived at their suggested diagnosis of SPS. It's why I was encouraging you to go back and ask for a full and detailed explanation of how they might have arrived at this diagnosis because dystonia is common with CRPS and it has to be ruled out before a diagnosis of SPS can be reached.

I had assumed that in getting to the stage of suggesting SPS, your doctor had already ruled out the much more clinically likely prospect of dystonia, possibly combined with other movement disorders associated with CRPS like myoclonus. You have been posting about your muscle wasting for such a long time and i was under the impression that this was something your doctors were already involved in looking into. Dystonia can cause muscle atrophy but it is largely due to lack of ability to functionally use the muscles because of the movement problems.

The differential diagnosis is based on clinical examination, testing and physician experience. I am not a neurologist but your should be able to explain to you how and why they have been able to rule dystonia/SPS and the myriad of other neurological conditions that cause very similar symptoms in or out. He or she should be able to do that by reference to your individual presentation.

You mentioned muscle dystrophy in your last post. Muscle dystrophy isn't the same as muscle atrophy - muscle dystrophy is the process by which muscle cell death occurs. Unlike atrophy, it isn't reversible. It's one of the reasons that the old name for CRPS was dropped because the 'dystrophy' part was misleading. There are relatively few people diagnosed who actually undergo muscle death although muscle atrophy is relatively common.

I think I asked this before and I'm not making a judgement but if you aren't very physically active you will experience quite significant muscle atrophy and weakness all over your body and you will also have pain and stiffness when you do try to move. Muscle mass is lost at an average rate of 4% per week when activity levels fall. Dystonia, SPS and other similar conditions have symptoms that go way beyond atrophy, stiffness, pain on movement and weakness.

I'm only saying all this in case you are perhaps in the care of a physician who is trying something because he or she feels stuck with nothing to offer or isn't sufficiently experienced in this area. You may be embarking on a treatment option that has potentially horrific side effects for no good reason. SPS is a very rare, terminal condition, its not like CRPS (however bad we think that is) and although you've not posted much information, I really think the more I hear, the more you need to stop and take stock before you go through with this.

Having been in the position you are with suspected SPS and feeling desperate, I know its hard but you need to be clear about what has happened so far and how you've got to this point before you go any further. Just my opinion.

The reason he is going w sps is due to my symptoms and elevated gad65. I am not sure if I have md or atrophy. My legs and arms r getting thin and weak despite my almost daily pool exercise . Every day I do less because I'm so weak. It is difficult for me to hold a book without straining my arms and back, when I swim I can't turn my head to breath bc my back goes into spasms. I can no longer kick my legs in the pool. The muscle atrophy/dystrophy is very painful. I am also dealing w the rsd pain. I feel like no dr has been able to make sense of this and I am running out of time. The retuxemb won't be happening for a few months bc of insurance issues... Thanks for your input,,keep it coming!

Debbie

Forgot to mention
 

I tested positive for small fiber poly neuropathy via muscle punch biopsy.....

It's not unusual to test positive for small fibre neuropathy with CRPS. This is something that has been looked at in research and been found to be a feature of many patients clinical presentation. Some articles and doctors describe CRPS as a small fibre neuropathy condition. Most CRPS patients aren't tested for it because it would add nothing to the diagnosis - if you have CRPS there's nothing they can do about the neuropathy and doing the skin punches themselves are likely to be very painful, possibly inducing a spread or a worsening of the existing CRPS.

How long has this deterioration been going on for?

The kind of deterioration you are describing with your exercise could simply be the progression of the kind of dystonia that can 'normally' be found in CRPS. I'm not saying it is, just that it can be. Pool exercise isn't weight bearing and if you are very inactive the rest of the time it may not be sufficient to maintain normal muscle mass. I gradually lost all my ability to kick in the pool, to walk and to move my legs on a stationary bike. Ive never recovered that ability. The deterioration was initially very rapid and then progressed more slowly over about 2 years. i have significant muscle atrophy. I had an initial movement disorder spread pattern that was typical of both CRPS dystonia spread and SPS. As I said, all of the things you are experiencing 'could' be described by high levels of general inactivity.

As fMichael said GAD65 levels can be elevated in other conditions. Diabetes is one. In the SPS cases where it is found to be elevated its typically at very high levels, its elevated at much lower levels for diabetes. Not that it's found to be elevated in everyone with SPS.

I seriously recommend you do as much research as you can of your own into SPS and CRPS related dystonia to try and match your own experience with what is described for both these conditions. Look at as many sources as you can and I still think you need to take a hard look at your medical team to be sure that they really know what they are doing - for something like a serious presentation of CRPS dystonia and for SPS diagnosis you really would want to seek out neurologists who have some experience of These conditions and get a second opinion. I had to go abroad to do that and went to a global leader in this stuff. It was worth it.

TY
 

Who did u go to abroad?

Debbie
I don't feel comfortable posting that information publicly but I will certainly let you know privately if you wish. I will try and figure out the pm system on here but if you are already familiar with how to do it, pm me and I will simply reply to you with the information.

stiff person syndrum
 

first of all i am new to this site. let me tell you a little bit about my story. in 2004 i started having twitching in my leg muscles, then it got worse and worse. i ended up in a wheel chair, untill i was diagnosed in 2006 with sps. a baclofen pump was in stalled in front side of my stomach with a cather around my side that hooked up to my spine. my daily dose was 658 per day. i could now walk again and do as i want.it saved my life. before with out this my body would go into spasity. my leggs would lock up to a point where the bones would almost break inside. so i know about pain. any little noise car horn anything would trigger the spasity. every two months id have to have the pump refilled. on top of the sps i got diebetes 1 from this. 1-28-13 ill be 44 years old. i live on long island, my nero is in brooklyn. in 2010 i started seeing another nero. here on the island that was supose to know about sps and baclofen pumps. boy did i find out how bad i was wrong. the reason i started seeing him was because the trip to brooklyn was too long, and all he had to do was moniter the pump. the problem started in 2-2012. im sorry anything other than that will have to be pm's. but i will ad this beware of the doc's here on long island about sps. thanks.

Hi
 

Hi and thanks for your input. Can u pm me the doc u saw. Also how we're u diagnosed w sps?p
Thanks

Debbie

Ps...I run a support group if u r interested

Hi, I live on Long Island and I was wondering if you still run the SPS support group. I was officially diagnosed withSPS high Gad positive in Nov. 2014.
Thanks

My pcp has done a questionable diagnosis of sps on me but still waiting on neurological appt to confirm or ro, my gad was neg tho, but can be false positive or false neg he said. The muscle spasms suck at best, currently taking baclofen 20mg 3x a day for them but not working well

i've never heard of that syndrome so i can't offer any input on it but hope you are feeling better soon. take care.

Patty I'm interested in chatting with you about sps. If you are willing please message me thank you

Stiff Person Syndrome
 

First off, wanted to tell you that the proper name for this disease is stiff person syndrome, not stiff man disease. I am female as are many ppl who have this disease. It was once called stiff man but it was changed bc of this.
If your doc is calling it stiff man disease, that suggests to me he may not be very knowledgeable of it. I was diagnosed by a spinal tap. If I were you, I would kindly ask your doctor if he has ever treated this disease this before bc it is very rare, very serious and you need an experienced doctor. I had the blood test and it came back a weak positive, not to mention the symptoms I'd been having. But I'd never heard of this disease before. I also got a second opinion but it wasn't for lack of not believing the first doctor who diagnosed me with it.
Before I went on a med like the one you mentioned, I would want to be 100% sure I had it and the best way to do this is to have a spinal tap. But SPS doesn't generally start with full body muscle symptoms, unless you've had it for years and I would think it would have been diagnosed before it reached that level of severity. . There are a lot of diseases that that could be but then again if you have the GAD65 antibodies, that is usually an indicator of SPS.
I'm not sure what you mean when you say you tried IVIG and it "didn't work". IVIG is used mainly to slow the progression down and it is highly unlikely that you would (or a doctor) be able to tell if it is working or not for a very long time.
There are also several diseases that might show up in a spinal tap that may not in labs. But if this doctor is experienced treating this, then you need to get busy treating it! It will progress and believe me, you do NOT want it to. I know from experience that it is very painful and takes so much from your life that you want to find a treatment that works and asap. I'm not your doctor or a doctor so if he seems to know what he is doing then do what he thinks you should. I wouldn't stick with him if he has never treated it before. The doctor that found mine had to refer me to a doctor that had more experience with it. He told me that and I know he was doing what was best for me.
Good luck. I can't tell how old this post is so if you've already resolved all of this, sorry and the best to you.

Hear me out on this SPS question, please
 

If you are still connected to this post, I feel SO MUCH for you with this diagnosis. I am writing because I tested a low positive for the GAD65 antibody, am already on IVIG for Myasthenia Gravis, and supposedly because of this have a crazy IGG ratio. I was referred to the SPS Clinic at Hopkins, because I have been having terrible, increasing spasms for over a year now. Of course Hopkin knows their stuff, but your case here perked my interest. Were you diagnosed by spinal tap? Everything else other than GAD in blood and IGG, and IGG ratio in spinal fluid looks great, yet I have maxed out my baclofen dosage, and the later I get in my IVIG cycle, the worse the spasms are. This IGG stuff has been blamed on Myasthenia Gravis. Does any of this sound alarming to you? All my best wishes that you are able to get some relief.

Deb, it sounds to me like you have RSD or the crap name of CRPS.
RSD is where the sympathetic nervous system generally from a crush injury gets stuck in over drive. It will go full body, via down the spinal column to affect all limbs. When I have a situation either physical assault or emotional, my body will freeze up. The freezing up is the sympathetic and autonomic nervous systems we don't control doing their thing.

I would find another doctor, preferably an anesthologist as they are the ones that treat RSD/CRPS. Like all doctors, some are good, some are bad. So best to ask around your area to try to find the best one. They generally work in pain clinics.

It might be good to explain how this started if you know. Generally people get RSD from a crush injury to the ganglion nerve and the body does not recover. Or a permanent cast on and when the body swells the cast is too tight ( crushing the nerve). But I do know of people who do not know how theirs really started...