Investigating Isaacs Syndrome: Study

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SirTrouserz

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A friend here gave me a copy of this study and it's pretty interesting. The information is put together a little differently than some of the others:Department of Neurology, Mayo Clinic and Mayo Foundation, 200 First Street S.W., Rochester, Minnesota 55905, USA. Neuromuscular hyperexcitability is a characteristic of Isaacs' syndrome. Autoantibodies specific for voltage-gated potassium channels (VGKC) or ganglionic nicotinic acetylcholine receptors (AChR) are markers of this disorder. To determine the frequency of these ion channel antibodies and of related neuron- and muscle-specific antibodies in patients with acquired neuromuscular hyperexcitability, we tested serum specimens from 77 affected patients (35 neuromyotonia, 32 cramp-fasciculation syndrome, 5 rippling muscle syndrome, and 5 focal neuromuscular hyperexcitability) and 85 control subjects. Among study patients, 14% had coexisting myasthenia gravis, and 16% had an associated neoplasm. We found that 35% had VGKC antibodies, 12% ganglionic AChR antibodies, 16% muscle AChR antibodies, and 10% striational antibodies. Overall, 55% had serological evidence of neurological autoimmunity compared to 2% of control subjects. Patients with neuromyotonia were more frequently seropositive (71%) than patients with cramp-fasciculation syndrome (31%). We conclude that acquired neuromuscular hyperexcitability consists of a continuum of clinical disorders with a common autoimmune pathogenesis. Copyright 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 702-707, 2002 FYI on the term seropositivity:Seropositivity: is the presence of a certain antibody in a blood sample. A patient with seropositivity for a particular antigen or agent is termed seropositive……It is also used (though less frequently) to refer to Rheumatoid factor.
 
not sure how to take these posts, you could take it as 14-16% of us may have an underlying neoplasm or myasthania gravis? if that was the case it seems all the people over the years here, one would have at least reported this?me thinks something else for me to worry about.
 
If you pulled 77 people out of the general population I am certain 1 or 2 might have a neoplasm, likely benign or possibly malignant somewhere in their body. So what is this saying? I have read that neuromyotonia may be caused by a neoplasm in the lung or thymus region. That being said true neuromyotonia can be diagnosed by EMG. Further to that there is no indication of age or any indication of what was found in the control group. I myself was not told I have neuromyotonia I was told I have benign fasciculations. Is there a difference? I don't know maybe someone more educated in medicine can answer that question.
 
From what I understood from one of my neurologists, the incidence of lung cancer is associated more with Lambert–Eaton myasthenic syndrome which has different symptoms, including muscle weakness, than the symptoms associated with BFS/BCFS/PNH. My neurologist said that he came across only one case of lung cancer in his 20 years of practice and he did not think I had it based on my BFS symptoms. I asked for and got a lung CT anyway and it came out fine.That said, there is no reason I can see that anyone who has BFS/PNH symptoms should not be getting a VGKC test as part of their treatment. Swift_TaySwift20 gave me some very good information about it. It's not that expensive and your doctor can order from the following site:For most people here I believe BFS is probably just an autoimmune condition that was triggered for one reason or another, but understanding how many of us have VGKC antibodies would be valuable regardless. If BFS could be indicative of paraneoplastic disorders, than that's just all the more reason why neurologists should be taking us seriously in regards to follow-up and treatment. Kit should be turning up around here too sometime soon though to weigh in on all of this. :D)Thanks for the encouragement Ron - I really appreciate it.
 
Good point Paul. These conditions are different. Because PNH as an autoimmune condition in rare cases can be indicative of an underlying condition though it should be monitored closely and is why we should have VGKC testing as part of of standard course of care.
 
Stevepaul has more studies available and information at , but this exerpt from the site clears up some of this issues, I think.Brain, Vol. 125, No. 8, 1887-1895, August 2002© 2002 Guarantors of Brain Phenotypic variants of autoimmune peripheral nerve hyperexcitability Ian K. Hart1, Paul Maddison2, John Newsom-Davis2, Angela Vincent2 and Kerry R. Mills3 1 Neuroimmunology Group, University Department of Neurological Science, Walton Centre, Liverpool, 2 University Department of Clinical Neurology, Institute of Molecular Medicine, Oxford, 3 Department of Neurophysiology, King’s College Hospital, London, UK Correspondence to: P. Maddison, Neurology Department, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UKReceived March 12, 2001. Revised February 18, 2002. Accepted February 22, 2002."Issues of practical importance arise from the strong association between PNH and immune-related diseases, such as myasthenia gravis with thymoma or lung cancer. First, our findings suggest that all patients presenting with acquired PNH should have a serum autoantibody screen that includes VGKC and AChR antibodies, plus glucose and thyroid function tests to help exclude other autoimmune diseases. Secondly, because PNH can be paraneoplastic, it is important to search for an underlying thymoma or lung cancer. Although nerve hyperexcitability presented in most of our thymoma patients after the tumour had been diagnosed, in the remainder the development of the neurological disorder might have enabled earlier identification of the neoplasm. Patients developing PNH over the age of 40 years who are seropositive for AChR and VGKC antibodies are most at risk. Eighty per cent of our thymoma patients had VGKC antibodies detected by the 125I--dendrotoxin immunoprecipitation assay, suggesting that the assay may be particularly sensitive in this subgroup of PNH patients. CT imaging of the chest should also be considered for patients who are cigarette smokers. In our patients, the lung tumours presented up to 4 years after the onset of nerve hyperexcitability. This long latency is also seen in the Lambert–Eaton myasthenic syndrome where small cell lung carcinoma can declare itself up to 4 years after the neurological disorder (O’Neill et al., 1988). Serial CT or chest MRI should be considered in high risk patients, i.e. cigarette smokers with late-onset PNH."
 
I smoked for 20 years. When I first went in for my twithcing the doctor sent me for a load of tests, most of which I have no idea about. He also sent me for a chest xray. So should I be going for a CT scan of my chest? I had one 2 years ago because of a different problem and it was fine.
 
One of the things that makes this condition so difficult is that it is apparently so rare that not many doctors know that much about it and some of the associated risks. And as rare as BFS/PNH is, the incidence of thymoma is even more rare than that, with only a very small portion of people going on to develop it or discovered to have it already. I believe that in the majority of cases of neoplasm, PNH/BFS/BCFS and myasthenia gravis are found together and according that occurs in only about 8% of those studied. Myasthenia gravis is associated more with neuromyotonia than with PNH/BFS/BCFS.I don’t like to take chances myself though which is why I asked for a Lung CT. My neurologist kind of rolled his eyes at me and told me he didn’t think I had lung cancer. My Lung CT was fine, but I may ask if I need one again next year depending on what my symptoms are like.I think what we need to ask for are the treatment and follow-up specified in the above study.1. First, our findings suggest that all patients presenting with acquired PNH should have a serum autoantibody screen that includes VGKC and AChR antibodies, plus glucose and thyroid function tests to help exclude other autoimmune diseases. 2. Patients developing PNH over the age of 40 years who are seropositive for AChR and VGKC antibodies are most at risk. Eighty per cent of our thymoma patients had VGKC antibodies detected by the 125I--dendrotoxin immunoprecipitation assay, suggesting that the assay may be particularly sensitive in this subgroup of PNH patients. CT imaging of the chest should also be considered for patients who are cigarette smokers. In our patients, the lung tumours presented up to 4 years after the onset of nerve hyperexcitability. This long latency is also seen in the Lambert–Eaton myasthenic syndrome where small cell lung carcinoma can declare itself up to 4 years after the neurological disorder (O’Neill et al., 1988). Serial CT or chest MRI should be considered in high risk patients, i.e. cigarette smokers with late-onset PNH.Because our numbers are so few and this so rare, I believe we have to be fully engaged with our doctors and looking out for our own health by discussing these issues with them. That’s my feeling anyway. I hope that helps Paul. Sir_Trouserz
 
Ok so here I am - ;) It is important to understand that many of these disorders deal with destruction of muscle and or nerve receptors hence the clinical muscle weakness etc. LEM is not a common disease nor is paraneoplastic syndrome but trust me when I tell you that it is well known to all physicians and especially neurologists, which is why every Myasthenia patient is sent for a lung/thorax CT to rule out lung cancer (specifically small cell) and thymoma.What we seem to forget on this site is that we can not diagnose etc in a vacuum. While it is true that there is alot unknown about this condition, there is a lot that is known about the many things that this condition mimics. So when you are examined and when you have your labs and when you have your EMGs, while your doc may not be familiar with BFS or BFCS they are in fact familiar with neuromyotonia, ALS, MG, MD, channelopathies, lung cancer, thymomas, paraneoplastic syndrome, LEM etc. Your labs and the examination is going to give further clues to alot of other conditions.If your doctor has given you the ok that there is nothing malignant going on and by malignant I mean anything that is causing active destruction of cells then you can be comforted even if you have not been given an exact BFS diagnosis. Finally and not to worry anyone, if there is no destruction to the muscles ie CPK levels then it is highly unlikely that a VGKC is going to show up as positive. Remember also that we can't do CPK levels in a vacuum either because if you have worked out, or had an injury then these may show up as high. We need to use caution here, medicine and diagnosis is NOT a chinese menu, one of this, one of that etc. It all fits together. If your labs were good, if your EMG is good or if you haven't had an EMG and your clinical exam was good you can rest easy that you are well and very likely have BFS or BFCS. If anything changes you should get checked out - remember having this doesn't mean you are immune to injuries or other conditions. It is likely an excellent idea to have a yearly check up, for more than this.So while studies and rare labs are wonderful sources of information remember there is a lot that is known about the body now and you can use what is available for diagnosis of even this condition. Kit
 
Thanks for all that Kit. My neurologist told me that my BCFS was due to anxiety though and it turns out that I have Cramp Fasciculation Syndrome, so I'm not taking any chances myself from here on out. I think I'll ask for a Lung CT for myself for the next few years to be on the safe side. There are just too many questions in my mind about their understanding of this condition. It's always good when the Doc weighs in though. :D) Sir_Trouserz
 
Sir_Trouserz,What makes you believe one neuro over the other? Did you have a specific test done that confirms Cramp-fasciculation Syndrome? Or did one neuro have better bedside manners? Just wondering.
 
Hi Vanessa!My son is home 'sick' (watching cartoons) so here I am online all day. The difference between the neuros is that I developed painful cramping in my feet and need to be treated for it. Dr. Tahmoush will treat me for this condition and the other one won't. If the pain can't be treated and the pain continues, then other things may have to be examined as a cause. The EMG that Dr. Tahmoush gave me had the wires taped to the outside of my foot and leg as opposed to the needles stuck in. I don't know if the diagnosis process varied other than that and Dr. Tahmoush having done some previous research and having knowledge of the condition already. I want to know the state of my health, if I'm at risk for other autoimmune conditions, if there are other health risks we need to look out for down the road and follow my progress. Dr Tahmoush will help me with that. Take Care,Sir_Trouserz
 
Not to add to the confusion but I am perplexed by something here. The article referenced above indicated that 33% of those diagnosed with BFS/BCFS were seropositive (indicating autoimmunity, I take it). Does this mean that 77% did not test positive for autoimmunity? And if so, why is it then assumed that BFS/BCFS is most certainly autoimmune in nature? Those statistics don't match the hypothesis. It makes me wonder if even within the spectrum of BFS/BCFS (let alone PNH) there is not a wide spectrum of causality, with autoimmunity being active for some but not for others? The stuff about neoplasms and so forth was unsettling but thank you, Kit for pointing out what most of us tend to forget....that physicians know about the differential diagnoses and are ruling in and out possible explanations for our symptoms based on ALL our lab and clinical findings and are less likely to be focused on just one explanation than we are.
 
There is a noted insensitivity to the VGKC test, however it is useful not only for uncovering autoimmune issues for some, but some other associated risks. Sometimes a person will test negatively for the VGKC test at one point and then will test positively at a later date. Autoimmunity is certainly not the only cause of BFS/BCFS, but is certainly one of them. Autoimmune conditions are notoriously difficult to diagnose accurately a good deal of the time. Having knowledge of these issues is important from the standpoint of making informed health decisions and making your concerns know to your physician on a medical condition that little is known about. It's always better to know what the risks are and discuss them with your physician, as is appropriate. A Lung CT is the best and most effective way to uncover any lung issue to the best of my knowlegde.
 
Hi people:Good info Sir_Trouserz, thanks. I had a white blood cell count test done when I first started with this desease even before I was officially diagnosed with BFS, I thought that a normal white blood cell test was an indicator of no cancer. Was the white blood cell count test only an indicator for some cancers?Mike C
 
Hello all,I have been taking a break from the board as I need to get my head straight. I still worry a lot. I have to say I am concerned about this post. I don't think I fully undestand it as I have no medical background. I never was told that I should have blood work. I was told I was fine by two neuros. I smoked up until 4 months ago. Do I need now to worry about another thing like cancer. None of 2 the neuros ever even mentioned that.Do I need bloodwork and that other stuff now?Any advice would be appreciated.Thank you,Luke
 
I guess it's very much a personal choice; I, for one, barely notice any twitching these days and wonder if I'd even be diagnosed with BFS if I went through the same testing again now.Given what I do know - the apparent odds of different outcomes, the effect that health anxiety and worry about BFS had on me for a couple of years, and so on - I personally choose not to go through any more testing at this point. Others will think differently, as is their right.
 
My neurologist said that he came across only one case of lung cancer in his 20 years of practice and he did not think I had it based on my BFS symptoms. I asked for and got a lung CT anyway and it came out fine.Sir_Trouserz, IMHO one should be very careful pursuing CT scans of the lung or any other body part due to the possiblity that the neoplasm will actually become a reality from the extreme amount of cumulative ionizing radiation. In fact there are indications that a CT scan of the thoracic or abdominal area is equivalent to approximately 500 chest X-Rays! Keep in mind that radiation is cumulative and over time can cause lung cancer and leukemia. This is the problem when our health anxiety overwhelms our good judgement resulting in our pursuing myriad invasive testing that at the end of the day may do us in.
 

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