Diagnosis of neuropathy--the (often) long search for a cause
 

Neuropathy, whether stemming from disruption of one or more peripheral nerves (actual "peripheral" neuropathy) or from disruption of nerves in the brain or spinal cord (which can happen through conditions like multiple sclerosis or mechanical compression), is a very hard conditini to pin down, there are over two hundred KNOWN causes of nerve damage--not even getting into those medical science has not yet identified. Some of these are secondary to other well-known condtiions, such as diabetes, thyroid dysfunction, or autoimmunities; some of these are primary conditionios of damaged nerve. In any case, since neuropathic symptoms can be produced anywhere in the body by problems of the brain and spinal cord, problems of the peripheral nerves, or both, the diagnostic process can be long, costly, and very often fruitless--at least a quarter of all people with nerve dysfunction wind up being labelled "idiopathic".

That being said, there are diagnostic protocols out there that should be followed. These can get lengthy and expensiive in many cases, and not all insurances cover all tests; one often has to decide just how far one wants to go in testing if one does not discover the cause of one's symptoms quickly.

Some sites that help provide source material for people to talk about with their physicians:


http://neuromuscular.wustl.edu/naltbrain.html

This is the diagnostics entry point for the huge neuromuscular conditions database at Washington University of St. Louis' medical website. It is written primarily in outline form, and mostly for medical professionals, but it is extraordinarily comprehensive; going through the links and sub links reveals a wealth of info on neuropathy (and other neuromuscular conditions). There are parts of each sub-section that are titled "Laboratory", indicating what tests might reveal that particular condition, as well as listings of signs/symptoms that might point to that particular diagnosis.

http://www.aafp.org/afp/980215ap/poncelet.html

The famous Poncelet protocols. The paper is titled "An Algorithm for the Evaluation of Peripheral Neuropathy". Outside of neurology textbooks, this article has become the "gold-standard" guidleine for many physicians and neuros for investigating the causes of potential neuropathies. The flow charts are particularly instructive (and good to show ingorant physicians).

http://www.thecni.org/reviews/13-2-p07-treihaft.htm

One of the best articles I know written about small-fiber neuropathies, which can be difficult to diagnose, as "standard" tests for neuropathy often come up "normal" and fail to reveal them (and meanwhile patients suffer). The reference list is excellent--it includes many of the seminal papers on skin biopsy, autonomic testing, and small-fiber vasculitis and other causes of small-fiber dysfunction (these can themselves be investigated if one wants).

http://www.questdiagnostics.com/hcp/...eralNeurop.htm

A small but dense clinical application paper about laboratory tests to investigate causes of peripheral neuropathy. Dr. Latov heads the Cornell Weill Center for Peripheral Neuropathy in New York City, and he and his staff may be the world's leading experts on immune-mediated neuropathies (not that they're slouches in other realms, either). (All docs there are both researchers and clinicians--and, I can tell you from personal experience, and informed patient can have great discussions with them.)

http://www.neuropathy.org/site/DocSe....pdf?docID=944

Another Latov paper, this one from the neuropathy.org website (the site of the Neuropathy Association), that specifically discussed the diagnosis of immune-mediated neuropathies, a category that most non-specialist physicians are not well-versed in.

http://www.dcmsonline.org/jax-medici...uropathies.htm

Another good paper--this one form Dr. Alan Berger and his colleagues at Jacksonville Shands. It provides a good overview of diagnosis and treatment options for various kinds of neuropathies, and suggests a particular categorizing method to understand them.

And, of course:

www.lizajane.org

This is a wonderful spreadsheet series that was put together by our very own LizaJane, with input from a number of other people who frequent Neurotalk, and designed to be as comprehensive a listing of possible tests for neurological conditionos, both central and peripheral, as our minds could collectively come up with. Broken down into symptomological sections, and with space to track test results over time (to look for patterns), it's wonderful for suggesting avenues to physicians and for noticing changes that might provide diagnostic clues.

And here's a really nice organizing chart--
 

--that cycelops found on the Washington University at St Louis Neuromuscular Disorders site:

http://neuromuscular.wustl.edu/over/...alwebn2ie2.pdf

Definitely suggests various testing options as it goes.

Another list:
 

This is another listing I found today, looking for the topic:

Drugs that cause PN.
This list is for all causes, and it is really something to see:

http://www.wrongdiagnosis.com/p/peri...thy/causes.htm

I will be starting a new thread on just the "drugs" soon.

Dear Mrs D - and hopefully Glenntaj will read this too...

I had the preliminary visit with doctor who will do the skin biopsy to me (he is the co-author of a paper which glenntaj posted in one of his posts - from Shands Jacksonville).

I will have my skin biopsy on march 26. He told me that I will have to take antibiotics after. After reading your thread on antibiotics causing neuropathy I am concerned taking any antibiotics.
In your opinion and glenntaj's too, is it necessary to take the antibiotics or can I forego or are there antibiotics that are "safe" to take without affecting the nerves?

I appreciate your feedback.

Btw, the neuro asked me to take glucose tolerance test. I don't if this will help, I have never had problems with my sugar. Will update you.

Thanks again.

Antibiotics
 

are one of the causes, Mrs. D., you have stated in the past. I am having a procedure tomorrow at 12:30p.m. and will be given antibiotics afterwards. Unfortunately, after Cystocele surgery about 3 1/2 years ago, i was given a script for Levaquin. I understand this one of the culprits. I will check in the a.m. for other antibiotics to be on guard against since I will be getting a script tomorrow.

Thanks,
(Ger)

Usually for skin/surgical procedures they give Cephalexin (Keflex) or another newer version of it. Or Augmentin.
These don't show up on lists as neurotoxic. However...the penicillins used LONG term like for Lyme, may have consequences long term on mitochondria. Short term use however, should be ok.

I'd clean those areas well for several days, with rubbing alcohol as well, to prevent any staph infections.

It is interesting--
 

--that they are having you take antibiotics with the skin biopsy; do they sense you are prone to infection for some reason?

With all the skin biopsies I've had, never were oral antibiotics involved; they simply gave me topicals to apply to the area for a few days after the little bandages came off. The skin samples taken are so small and shallow that there is little chance of infection, I think, in non-immunocompromised individuals.

I think it is the fear of MRSA and staph that seem to
infiltrate clinics and hospitals. Even the staff who do the procedures may be carriers.

I think cleaning the skin well, before the procedure is important.
This is one concept that plastic surgeons prep carefully.

Glenntaj
 

While reading some posts on skin biopsy, my understanding was : with skin biopsy, there might be chances of detecting cause of neuropathy that could not be detected in the bloodworks. This was told to me also by my earlier neurologist. Yesterday, during my initial visit with the neuro who will do the biopsy, he mentioned that the objective of the biopsy is to determine the presence of Small Fiber Nerve Neuropathy. After leaving the clinic, I remembered what my previous neurologist said about the possibility of finding a cause of neuropathy in the skin biopsy. I called the neurologist today and clarified my confusion. He confirmed that the only purpose of the skin biopsy is to determine whether I have a Small Fiber Nerve Neuropathy or not. He even added that he disagrees with what my previous neurologist said. He told me that it will still benefit the patient to take the skin biopsy for official diagnosis and what to do next.

I am confused with the contradicting statements. Though, I am being realistic with my expectations on the result of the skin biopsy, but I am still holding on to a thread of hope that something is causing this neuropathy.

Having had several skin biopsies yourself, I am hoping that you could enlighten me.

Thank you so much.

I will take note of the name of the antibiotic you mentioned.

I will clean the areas very carefully after the procedure....what about cleaning it with hydrogen peroxide?

Oh, I am so glad that you are not taking either Gabapentin or Lyrica. Even how seemingly confident the doctors say about the safety of these medicines, but in the long term use, it will have side effects on the total well-being....that is what I am worried about. But, right now Mrs. D, it will be totally unbearable if I dont take Gabapentin. I hope the supplements will do me good just as they do good to you and to others. I am sad that I could not take the R-Lipoic at this time due to my abnormal thyroid function. I have been now referred by PCP to an endocrinologist to manage my thyroid.

Thank you so much..... :)

Unfortunately--
 

--while skin biopsy is excellent at documenting the density and condition of the small fiber sensory nerves, it is unlikely to reveal a cause of any damage or reduced intraepidermal nerve fiber density that may be found and documented.

There are some clues that might be revealed--swelling and or "exploded from the inside" fibers might hint at an inflammatory or autoimmune process. But the samples are generally too small to collect appreciable lymphocytic infiltrates from, or to collect cytokines from (both of which might confirm an autoimmune process). And, generally, the samples are not cultured to reveal if there is a direct viral attack to the nerves (though I imagine this might be doable).

One thing that can be tested for is the presence of amyloid (my samples were--negative). This is an extraordinarily rare situation, though (literally about one in a million).

To Mrs. D and Glenntaj,
 

The neurologist who did the skin biopsy called me a while ago and told me that my result was normal. I felt relieved but very confused at the same time.

I asked if there are any more tests that I should do to explore other conditions. He said none and I should just continue my Gabapentin and observe my symptoms until my next appointment with him.

I am now so confused that with all the pain I have been through, and still going through, which are very typical of a PN, what condition do I possibly have? What do you think should I do next?

Thank you in advance for your help.

Is there an illness that mimic the symptoms of a Peripheral Neuropathy? I ask this question because I know the pain in my feet, stabbing pins and needles in both arms and legs, numbness in my two big toes are not just in my mind. I know that I could not wear even a pajama because just a mere touch of it causes so much pain. Having said that, what else should I do to pursue my "saga" in finding what is wrong with me.

The doctor seems to think that this is the end of the line for me, after having a negative result of the skin biopsy.

Will appreciate any suggestions/feedback.

Thank you.

Not every skin biopsy--
 

--is unequivocally positive even in people with symptoms of small-fiber neuropathy.

A lot has to do with the extent of the damage, and exactly from where the samples are taken. Damage can be patchy, or the "normal" figures given for intraepidermal nerve fiber density--anything withing the fifth to ninety-fifth percentiles--may technically be designated as normal, but not be normal for you (it's almost impossible to know at what level one started before symptoms).

Do you have the report yourself, to relate to us?

Also, while skin biopsy is the gold standard for small fiber syndromes, there are some other (older) tests that are sometimes used, such as qualitative sensory testing and certain autonomic tests, such as quantitative sudomotor axon reflex testing (QSART), which measures the sweat response of small skin fibers.

There are certainly other conditions that can mimic small-fiber symptoms--circulatory dysfunction and central nervous system problems (such as central nervous system demyelinating syndromes) among them--what other testing has there been for these?

Dear Glenntaj,
Thank you so much for your reply.

The samples were taken from two spots (left leg) : 1) thigh, and 2) just above my ankle.

I dont have the report with me but I could get it from the clinic. I will post it here once I have the report.

I mentioned the QSART to my neurologist when he did the skin biopsy and his response, more or less, was: "I am not so inclined on that test. Its just a sophisticated sounding test but its not much of a help. I could diagnosed you with autonomic neuropathy if your blood pressure goes down when you get up from a lying position."

The only test that I know that may involved the central nervous system was the MRI of my head. I am not familiar with central nervous system demyelinating sydromes. I will have to google it so I can understand what you mean.

Is there a published paper about a negative skin biopsy result but manifesting the PN symptoms? I am asking so I could better discussed with my doctor. Right now, I have the impression that he is no longer giving me further tests.

THank you for your help.

I failed to mention that I also had MRI of my cervical spine and lower extremity doppler.

These are the CNS demylinating diseases that I found on the net:

Multiple Sclerosis - (according to my doctor, based on the head MRI, I dont have this.)
Optic neuritis
Devic disease (neuromyelitis optica)
Transverse myelitis
Acute disseminated encephalomyelitis
Adrenoleukodystrophy and adrenomyeloneuropathy

I dont have symptoms of any of the above conditions, except that I have dry eyes. But, I dont have Sjogren's syndrome.

Thanks again!