Peripheral Neuropathy and MGUS

[misswoosie]

Hi, new here. I have peripheral neuropathy caused by an autoimmune disorder- IgM MG with MAG antibody.

I was eventually diagnosed with Monoclonal gammopathy (MG) about 4 years ago after a year of complaining of unusual tiredness, balance problems, joint pain and several skin and gum infections.

MG, which is very common,especially as we get older, is when the B cells in the bone marrow produce a clonal (abnormal) immunoglobulin protein known as a paraprotein. People with SLE, Rheumatoid arthritis, Coeliac,etc etc may have MG's

Sometimes the cells produce a very high amount of the abnormal protein and the MG can progress to types of cancers such as Multiple Myeloma , Waldenstroms , Non Hodgkins Lymphoma and Amyloidosis ,amongst others. The risk of progression is fairly low at about 1-2% per year, but it's a bit like sitting on a ticking time bomb when you have it, especially when it's often described as a condition that has no symptoms, which, having spoken to a lot of people who have it and have symptoms, is frankly a load of rubbish!

Danger signs that things may be progressing include Anaemia, altered kidney/liver function, enlarged lymph nodes and bone pain etc and also increasing levels of the paraprotein

There are 3 main Immunoglobulins- IgG, IgA and IgM and my paraprotein is in the IgM. Because my IgM is mostly abnormal proteins , and also because the condition suppresses the other 2 immunoglobulins, I'm prone to mainly skin , gum, sinus and eye infections. I don't mix with children or in big groups ,but I'm sure if I did I'd catch everything that was going.

Neuropathy can be associated with a paraprotein in any of the 3 immunoglobulins, but it's more common with IgM.

Shortly after I was diagnosed I mentioned to the Haematologist (who's quite disinterested as my abnormal protein levels are very low and I don't have any of the danger signs) that I had tingling in my right foot and often felt like I had something stuck to the bottom of it.

He tested me for an antibody that can be associated with IgM MG and my level was 8000 with the normal being less than 1000.

The antibody is called MAG (Myelin Associated Glycoprotein) antibody and is very rare, affecting only 1 in 100,000 people.

The antibody attacks a protein -MAG- which is essential to normal myelin, which is the insulation around the peripeheral nerves. The lack of healthy myelin results in the electrical nerve impulses not reaching their target, and it's a length (of the nerve) dependant neuropathy so usually starts in the feet and moves upwards and becomes more severe as more of the myelin is gradually destroyed. Evntually it may spread to the hands and arms, but everyone is different with speed of progression.

It's similar to Multiple Sclerosis except that the spinal and cranial nerves aren't usually involved.

Symptoms can be treated with anti depressants and drugs like pregabalin and gabapentin, but they often have side effects

Regarding trying to reduce the levels of the antibody and slow down or halt the progressive neuropathy, because it's a rare disorder, and not a lot of research has been done,there's not really a consensus regarding which people to treat, when to treat or what to treat with. Some of the possible treatments are IV Immunoglobulin or drugs used in the treatment of cancers such as Rituximab, but all have the potential to affect the immune system and it seems some people (maybe 20-30%) respond to treatment, whilst others become worse but the majority have no change.

It seems that many neurologists /haematologists doctors are reluctant to treat at all or wait until the person is quite severely disabled. The leading experts (in the UK are in London at the National Neuromuscular Centre) suggest that people should be treated early on, as once neuropathy has been present for 2 years it's irreversible, so waiting until someone is disabled to treat is like shutting the stable door after the horse has bolted.

PLEASE NOTE I'M TALKING ABOUT TREATING THE ANTI MAG NEUROPATHY HERE, NOT THE CANCERS THAT MG CAN PROGRESS TO.

MG is commonly called MGUS -which (rather dismissively) stands for Monoclonal Gammopathy of Unknown Significance, but recently the term MGCS has emerged. This stands for Monoclonal Gammopathy of Clinical Significance, which is what people with MAG antibody can be classified as having.

Anyway, that was a long post. My neuropathy is gradually progressing, but I'm in a much better boat than some people with Anti MAG neuropathy.

Wondering if there's anyone else out there who has MAG antibody or MGUS and peripheral neuropathy. I also have all the symptoms of Sjogrens which is also an autoimmune disorder.

[RobieC]

Thank you for this information

misswoosie!! I was initially diagnosed with fibromyalgia- about 6 years ago; then RA, chronic fatigue, and the list goes on... But, I do suffer from neuropathy in my feet for which an explanation has never been offered (And honestly, I never asked for). Your post however, gives rise to a potential cause regardless of its rarity. One question though, do you know if MAG/MGUS tends to run in families? My father also neuropathy, quite severely, with no explanation as to why. Thanks again, this is very interesting!

[misswoosie in reply to RobieC]

Hi RobieC. Yes, if someone in the family has MGUS then you're more likely to have it.

My Mum who's 82 has peripheral neuropathy for abut 15 years. She has virtually no sensation at all on the bottoms of her feet and has worse problems than me with her balance. Also numb finger tips, which makes it very difficult for her to pick small things up.

She isn't diabetic but does have extensive osteoarthritis in her hips , spine ,shoulders etc however, her neuropathy is typically length dependent ie started in the places that are furthest away from the spine where the sensory nerves originate.

Nobody except the physio' who saw her at the Falls clinic (after the consultant had seen her and then sent a letter saying she didn't have a significant neuropathy!) and me seem concerned about it. I have it on my "to do list" because she is my Dad's main carer and they're both becoming less independent.

She was told she had carpal tunnel syndrome about 4 years ago and had surgery on her right hand, but although she had a slight improvement to her sensation, it made the neuropathic pain worse.

I have IgM MGUS and associated Anti MAG antibody (Anti MAG isonly found with IgM MGUS) but the other 2 more common categories of MGUS , IgG and IgA, can also cause neuropathy including CIDP which is an inflammatory neuropthy with a slightly different presentation and symptoms..

MGUS are often found alongside auto immune conditions like RA and a lot of people who have MGUS a have previously been diagnosed with things like Fibro and CFS.

I only have a diagnosis of MGUS and Anti MAG neuropathy and MGUS on it;s own is supposed to be symptomless (even Myeloma UK website says that) but I can tell you (as can a lot of other people who have MGUS) that common symptoms include extreme fatigue and joint and muscle pains.

Maybe you can ask for a referral to a neurologist? Blood tests can check if you have MGUS/MAG Antibody and a test called a electromyelograoh can help to diagnose neuropathy and indicate what type it is.

[orange33]

Hi just beginning to understand this awful condition. Not had much help from GPOr RA Docs. It's been life changing for me.

I must admit it is difficult to explain to family i have this condition. I am greatful though to my Nuero Doc for trying to help me.

Wish you all well.