New Treatments for Neuropathy (Part 1)

Edited Chat on www.virtualnurse.com/Chat/Diabetes (no longer available)
Date: December 17, 1998, 10:00 PM EST
Host: Melissa Davis
Subject: Neuropathy
Guest: Dr. Aaron I. Vinik, Research Director, Leonard R. Strelitz Diabetes Institutes
Eastern Virginia Medical School

Mary from Ma.
Dr. Vinik, would you explain your protocol for treating neuropathy?

Mimi
Dr. Vinik, what is the latest and best treatment for this condition?

Dr. Aaron Vinik
The question on what our approach to treatment of neuropathy requires a fairly long answer, and I will try to do my best in as few words as possible.

It is important to realize that neuropathy is not one condition but many conditions that have different causes and therefore different treatments. Important examples are focal neuropathies that start suddenly without any warning and can result in a facial palsy, paralysis of other nerves throughout the body. These are due to vascular accidents where the blood supply to the nerve is interrupted and will heal spontaneously.

The entrapment syndromes, like carpal tunnel, or tarsal tunnel or wherever a nerve goes through a tight space are treated in the following manner: Simple resting of the wrists at night with splints is often helpful. A mild diuretic will often reduce the amount of fluid in the confined space in which the nerve is trapped and provide relief. Yoga stretching exercise can help, or even shots of steroids into the wrist. If all else fails,then surgery may be appropriate. The problem is that the diagnosis is often not made, and then the condition can go on to permanent damage so that little can be done for the nerves.

Then there is a form of neuropathy that affects the nerves to the thighs and the shoulders. We used to call this diabetic amyotrophy and believed that it would take a year or two to recover. We now know that this is not true, and the condition is often an inflammatory one, a vasculitis or even an autoimmune destruction of nerves. We have recognized that it is not a great leap to be able to introduce immune therapies into the treatment of this form of neuropathy.

The distal forms of neuropathy affecting the hands and feet and the autonomic neuropathies are another whole story.

Judy Reaves
Dr Vinik, I was a candidate for the study at Loyola near Chicago in October of '98 but turned down because I wasn't in bad enough shape. Now my feet are really numb with shooting pains now and again. Has the study been completed? Was it a success? Does it now have to be approved by the FDA? How long? Is there a name for the drug?

Dr. Aaron Vinik
The study you refer to being done at Loyola is being carried out in 1500 patients in the rest of the world and 1000 patients in the US. It is scheduled to end in March of 99. The FDA has approved fast tracking the drug if the study is successful, and we ought to be looking at the company making it available sometime after that.

Brad
Dr. Vinik, please tell me how low blood sugars can lead to neuropathy?

Aaron Vinik
When your blood sugar is low, a variety of symptoms can occur. Some people become sweaty, shaky, tremulous and have palpitations while others become confused, irritable, and may even go into a coma. A common manifestation of hypoglycemia is tingling around the mouth and lips, and sometimes this can affect other parts of the body. It is usually self-limiting and goes away when the blood glucose returns to normal. If however, you have recurrent severe attacks of low blood glucose, then the damage to the nerves can become more permanent. It is a good idea to try to eliminate too many low blood sugars.

Sandy Donchess
Dr. Vinik, are you saying that severe hypoglycemia causes nerve damage? I, too, have had lows that caused tingling in my mouth/lips. My son had a number of severe hypos (convulsions) during the night some years ago. He's 11 and was diagnosed at 4.

Dr. Aaron Vinik
Yes, severe repeated hypos can actually cause nerve damage, but they have to be severe and last a long time and occur repeatedly.

Mimi
Is there treatment more effective than that which I receive... hydrocodone when the pain is so severe I'm crazed. Tylenol at other times. There surely is something better...

Dr. Vinik, my newest "neuropathy" problem seems to be a nerve near one eye...double vision which lasts a few minutes. Comes about every 6 weeks, then goes away, then comes back for a couple of minutes.

Sandy Donchess
Dr. Vinik, can you tell me exactly what you mean by "severe?" In my mind, anything that involves the person being non-responsive, convulsing/twitching (glucagon time) is severe...

Mary from Ma.
Dr. Vinik...what exactly is the treatment you are using for neuropathy?
Does it vary??

Jane
Dr Vinik, is Neurotin being used for neuropathy pain?

Dr. Aaron Vinik
There are a lot of questions about the pain that occurs in diabetic neuropathy. The reason that many people live with their pain and do not respond to treatment is because the underlying disorder is not addressed.

When the neuropathy involves small nerve fibers and the pain is burning, and stinging with feelings of pins and needles and the very slightest touch makes it worse, then the right treatment is topical capsaicin or, clonidine starting with tablets taken at night. Neurontin works for this type of pain, too, and if these fail then using amitryptylline alone or together with fluphenazine will in most instances stop the pain.

When the pain is like lightning bolts, then the right treatment is tegretol which should really not be used under other circumstances.

When the pain is deep seated and nauseating, like a dog gnawing at the bone or like a toothache in the foot, the first line of treatment is an insulin infusion, not to lower the blood glucose, but insulin IV works to block this type of pain.

If the pain is in a nerve root distribution, then tegretol again is the right drug.

If the pain is associated with degeneration of the joints and bones of the feet, then we need to toughen up the bones and the treatment is with a bisphophonate.

These are a few examples to illustrate the importance of making the right diagnosis if one is to achieve resolution of pain.

Lynn
Thank you, Dr. Vinik, for the info regarding the different types of neuropathy. It certainly is helpful to be aware of the differences so I can ask for clarification from my physician to find the correct treatment.

Mimi
I can hardly wait to ask my doctor about tegretol for my severe Lightening Bolt stabbing pain.

Dr. Vinik, my double vision has been checked by my physician and my opthamologist, and they both say "neuropathy." Is this something to worry about, can something be done about it?

Ellen
My son has had diabetes and his left eye is sometimes droopy - diagnosis ptosis. I wonder if it has to do with the diabetes. The ophthalmologist said no, although he ruled out Horner's syndrome which involves a nerve in that area. Can some neuropathy be developing already just in that area?

He's had diabetes 10 years. He's 11.

Dr. Aaron Vinik
Ptosis can occur in diabetes. It may be due to Horner's syndrome if the sympathetic nervous system is affected, but this is an extremely unusual presentation of diabetes. Also, drooping can occur if the third nerve to the eye is affected in this case, the eye droops, and the eye itself tends to look down and out because the third nerve acts to move the eye in and up. When this occurs it is not usually a fluctuating course but will resolve with time. The most common cause is a vascular block, and nature has a way of stimulating the opening of other vascular channels that take over the function restoring blood supply to the nerve. Sometimes a droop is due to fatiguing of the eye that occurs in Myasthenia and other times simple fatigue. Some people do have lazy eye muscles and get transient blurring of vision,and it is not unusual to find it when the blood sugar is too low or too high. Blurred vision should however never be ignored and one should see the doctor about it.

Ellen
Thank you Dr. V. The ptosis seems to come and go. I'll mention this to the opthamologist during the 6 month follow up.

Melissa
Our doctor always says Kristina won't have complications this early! I get the impression that kids, no matter how long they've had diabetes, have a "clean slate" until their teenagers! and THEN the clock starts ticking! I have a hard time believing that though!

Ellen
My son's doc would completely refute that statement, Melissa. The clock starts ticking from the get-go and that's why high bgs need to be avoided right away. I believe this to be true.

Sarah
Melissa, my friends niece who is now about 14 has a completely numb foot from neuropathy. I don't know many details, but it doesn't sound like she has ever been in good control. I believe she was diagnosed before age 2

Sarah
I wish more doctors recognized the problems. I had pain in my right little finger for years before I finally was diagnosed so now probably have permanent damage.

Dr. Aaron Vinik
The clock starts ticking for people with diabetes when they are diagnosed if they are type 1 and long before they are diagnosed if they are type 2. The DCCT taught us that if you do not have complications of diabetes and intensively control your blood glucoses so that they are in the near normal range, that you can reduce the likelihood of developing neuropathy by up to 65%. This is important but not always easy to achieve. If you had pain for a long time in a finger before you were finally diagnosed that does not mean that the changes are irreversible. Pain is a good feature of neuropathy, it means that the nerves are alive and can recover. When you develop weakness or wasting of the muscles then it may be too late.

MAR
Dr. Vinik, you're assertion that the clock starts ticking up on Type 1 diagnosis presents an enormous and nearly untenable challenge for parents of young ones who fear cognitive losses or worse consequent to tight control. Have you any words of wisdom? Target A1C's? Also, (If you'll pardon my opportunistic greed!) do you believe each individual high bg has a damaging impact despite an overall favorable A1C?

Brad
Dr. Vinik, how much success have you had with the use of ALA, GLA and Acetyl-L-Carnitine? I've used these on the carpal tunnel or tingling in my hands and it seems to have helped a lot. Maybe just the placebo effect.

Dr. Aaron Vinik
What of GLA,alpha lipopic acid and other antioxidants. No, I don’t think your response was a placebo effect. There are now several studies in the literature that have documented improvement in nerve function with supplementation of the diet with gamma linolenic acid. The story with N acetyl carnitine is quite different. While very effective in rats, the major human study failed to show any benefit, and the company has elected to close down the study and terminate all activities with the compound.

Brad
Thanks Dr. I'll discontinue the use of the N acetyl carnitine.

Sandy Donchess
Dr. Vinik, I have had Type 1 for 30 years. I'm 41. I was diagnosed with rheumatoid arthritis almost 10 years ago. My wrists and feet are my weak points, and sometimes the pain is moderate. I take Naproxen, Plaquenil and low dose Methotrexate. How can I know whether neuropathy is the culprit, or rheumatoid arthritis?

Dr. Aaron Vinik
Pain in arthritis can be difficult to distinguish from neuropathy. The key differences are that there are findings on the clinical examination that clearly distinguish neuropathy from arthritis. Some causes of arthritis can also cause neuropathy then the two conditions can coexist. The treatments of course would be very different, hence the need to make the distinction.

Ruth
Dr.Vinik has any research been done on whether antioxidants help in the prevention and/or treatment of neuropathy. If so what ones? There are so many. Also, do you know if the antioxidant alpha lipoic acid has any effect on neuropathy?

Dr. Aaron Vinik
Are antioxidants useful for neuropathy? The answer to that is yes. There is now good evidence that if your blood glucose remains too high, then the body's natural antioxidants get used up and you get what is today being called a state of oxidative stress! To overcome this clearly, the best thing would be to keep the blood glucose normal i.e. a HBa1c of <6.05. This is not always possible. That is why antioxidants are being investigated for neuropathy.

There is now important information generated in Europe and England that alpha lipoic acid, a potent antioxidant can reverse or slow the progress of neuropathy. These studies were called the Aladin studies. Now in the US, we are testing this theory in studies referred to as the NATHAN studies, and we will have the answer somewhere down the road.

For the meanwhile, I think it is important for all people with diabetes to be taking an antioxidant mix if their blood glucose control is not perfect. If your pain goes away, that does not mean necessarily that the neuropathy has gone. It may mean that the nerves are getting better, but it could also mean that they are getting worse. When nerves are very badly damaged, then pain will disappear to be followed by numbness and loss of sensation(i.e. the disappearance of pain may herald deterioration). This is what the doctor may be telling you, and then you have a greater need to take care of your feet.

Sarah
Will neuropathy go away permanently or can it only be controlled?

Cyndee
I didn't get the answer to "Is neuropathy something that can be reversed for most people, or only some people?" Can it be reversed by good blood sugar control alone? Thanks for your patience, Dr. Vinik!

Sarah
Dr. Vinik, does neuropathy go away completely like an infection or only get under control like diabetes?

Dr. Aaron Vinik
Neuropathy in the past could only be slowed down but not reversed. We are now in a wonderful era, much like what is happening with pancreatic islets, in which we are capable of getting nerves to grow back again and we can reverse neuropathy. We have several examples of people who had lost sensation in their feet who can now feel even the texture of fine grains of sand or even a mosquito’s bite. We have the tools now to treat patients with nerve growth factors and recovery can occur. These are the drugs that are being investigated now,and with any luck,will be available for general consumption in the not too distant future. Other forms of neuropathy respond to immunotherapy, and people confined to wheelchairs have recovered. This does not mean that it will happen to everyone, but it does happen often enough now when we recognize the condition that we are becoming a lot more optimistic about it.

Dr. Aaron Vinik
Is neuropathy reversible in everyone or only some? A lot depends on the type of neuropathy and what part of the body it affects. Some forms are reversible in everyone for example proximal neuropathies and entrapments if caught early. Other neuropathies get better, but it may take several years.

When the pain goes, and you are left with wasted muscles, then the best thing you can do is do regular muscle building exercises and with some effort, you can rebuild the muscles. One of the important aspects of muscle strength building is the risk of falling when your muscles are weak and your balance is affected. People with diabetes and neuropathy are 17x more likely to fall than healthy people. This risk can be markedly reduced simply by doing muscle strengthening exercises. AIV

Ruth
Dr. Vinik this sounds so exciting for everyone suffering from neuropathy. Thank you for the dedication and hard work. The quality of life for diabetics is finally being improved.

Deb
Dr. Vinik,-- I am one of those who can now feel my feet after years in leg braces and wheel chairs -- my BG's are normal because of a pancreas transplant 5 years ago. My neuropathy is MUCH better, but I still have legacy muscle atrophy. I am doing physical therapy -- are there any new treatments that I should look into? -- I'm very anxious to find out about nerve growth factors. If I build my muscles up my balance will come back? I thought that was something to do with proprioception? You're right about the falling -- I fall at least 17x as often!! Very embarrassing.

Dr. Aaron Vinik
I am delighted that your neuropathy has responded to the pancreas transplant. If you are interested in nerve growth factors you could contact the investigators in your area or the company. E-mail me, and I will see how we can put you in touch with the right people.

Balance is a proprioceptive function. However, one can overcome many deficiencies with brute force. Strength in the ankles and thighs is a wonderful compensation for lack of proprioceptive input from the periphery. A wonderful study done in older people showed that there is a natural rate of decline in coordination and proprioceptive function after the age of 65 years. This can be shown with loss of vibration perception with the tuning fork that you see doctors test the feet with. It can also be shown to interfere with backward tandem walking and when severe, results in ataxia. By submitting to muscle strength building 3x/week with light weights these folks were able to develop strength and improve their backward tandem walking without a change in their nerve function. Down the road we are developing new drugs for these neuropathies that affect coordination and together with a muscle strength program, there is no reason why we should not be able to reduce the likelihood of falling.

Deb
Thank you so much Dr. Vinik. I will contact you.

Sandy Donchess
Thank you, Dr. V. One more question: how can I get a diagnosis as to whether the swelling/pain is caused by arthritis or by diabetic neuropathy? What would this entail?

Dr. Aaron Vinik
To distinguish between neuropathy and arthritis you need to see a generalist or a neurologist. Either should be able to tell the difference. Be sure to tell them what your question is. This will make sure they don't leave it unanswered. AIV

Sandy Donchess
Thank you very much, Dr. V.

Dr. Aaron Vinik
Thank you all for the questions. Happy to be of assistance and thanks Melissa for arranging these chats. Thanks for joining us in the chat room.
Good Night, God Bless.

Melissa
Dr. Vinik, thanks so much for coming tonight! You've helped so much!