Why Nerve Damage May Be Restored In Some Cases Vid

Today's video and explanation from medicaldaily.com (see link below) explains why nerve damage is almost always irreversible and in that sense is very useful. However, it could do with simple graphics to illustrate what she says (at breakneck speed!) and furthermore, she tends to concentrate on nerve damage as a result of accident or injury and in those areas, there is the possibility of some nerve restoration. The vast majority of neuropathy sufferers however, have the condition due to over 100 other causes than injury and for those people, nerve restoration is practically impossible. This video, while useful, tends to blur the edges a bit and can confuse you if your nerve damage comes from common causes such as diabetes of chemotherapy, or HIV or whatever. In cases where direct injury is not involved, nerve damage restoration is almost impossible at the moment (although stem cell therapy is offering hope).

Reversing Nerve Damage: Central Nervous System Inhibits Cell Regeneration, But Stem Cell Treatment May Help
February 27, 2016 12:12 PM By Lizette Borreli

 
Our nervous system is involved in everything our body does, from maintaining our breath to controlling our muscles. Our nerves are vital to all we do; therefore, nerve pain and damage can heavily influence our quality of life. In Discovery News' latest video, "Why Can't We Reverse Nerve Damage?" host Lissette Padilla explains the central nervous system (CNS) has certain proteins that inhibit cell regeneration, because each cell in the nervous system has a unique function on the pathway, like a circuit, and can't be replaced.

The nervous system can be divided into two sections, with the brain and spinal cord making up the CNS. Nerves are made up of sensory fibers and motor neurons, which comprise the peripheral nervous system. Nerve cells are made up of many parts, but they send signals through threads covered in a protective sheet of myelin. These threads are called axons.

Axons are the long part of the cell that reaches out to neighboring cells to send information down the line. Schwann cells, found only in the peripheral nervous system, are glial cells that produce protective myelin. Schwann cells could potentially clean up damaged nerves, which could make way for healing process to take place and new nerves to be formed.

The problem is these Schwann cells are missing from the CNS. The CNS is comprised of myelin-producing cells called oligodendrocytes. And these cells don't clean up damaged nerve cells at all, hence the damage problem.

However, research is currently underway to examine the potential success of system cell treatment, where stem cells are injected directly at the injury site. It will still take a few years to see the results of such trials, but since the peripheral nervous system doesn't have the same blocking proteins that the CNS has, the idea is Schwann cells could help heal the damage.

So it is possible to regrow nerves, albeit slowly. For instance, if you cut a nerve into your shoulder, it could take a year to regrow. By that time, the muscles in your arms could become atrophied. Researchers are working on helping the body heal faster.

http://www.medicaldaily.com/central-nervous-system-inhibits-cell-regeneration-stem-cell-treatment-375482

Why is Your Pain Neuropathy and Not Something Else

As always, every few weeks you'll see a general post about neuropathy here on the blog. Many people arrive at the blog with little or no information about what is happening to them and need a simply explained and accurate description of what their problem might be and how it may be treated. This very useful article from patient.co.uk (see link below) is exactly that. It's a U.K. article for a change and is a good basis from which to research further and ask questions of your doctors. However, even for experienced neuropathy patients, you may well read something here you didn't already know, or refresh your knowledge in some way (how many remember what nociceptive pain is for instance?)

Neuropathic Pain

Neuropathic pain (neuralgia) is a pain that comes from problems with signals from the nerves. There are various causes. It is different to the common type of pain that is due to an injury, burn, pressure, etc. Traditional painkillers such as paracetamol, anti-inflammatories and codeine usually do not help very much. However, neuropathic pain is often eased by antidepressant or anti-epileptic medicines - by an action that is separate to their action on depression and epilepsy. Other pain-relieving medicines and techniques are also sometimes used.

What is neuropathic pain?

Pain is broadly divided into two types - nociceptive pain and neuropathic pain.

Nociceptive pain

This is the type of pain that all people have had at some point. It is caused by actual, or potential damage to tissues. For example, a cut, a burn, an injury, pressure or force from outside the body, or pressure from inside the body (for example, from a tumour) can all cause nociceptive pain. The reason we feel pain in these situations is because tiny nerve endings become activated or damaged by the injury, and this sends pain messages to the brain via nerves.

Nociceptive pain tends to be sharp or aching. It also tends to be eased well by traditional painkillers such as paracetamol, anti-inflammatory painkillers, codeine and morphine.

Neuropathic pain

This type of pain is caused by a problem with one or more nerves themselves. The function of the nerve is affected in a way that it sends pain messages to the brain. Neuropathic pain is often described as burning, stabbing, shooting, aching, or like an electric shock.

Neuropathic pain is less likely than nociceptive pain to be helped by traditional painkillers. However, other types of medicines often work well to ease the pain (see below).

The rest of this leaflet is just about neuropathic pain.

What causes neuropathic pain?

Various conditions can affect nerves and may cause neuropathic pain as one of the features of the condition. These include the following:
•Trigeminal neuralgia.
•Postherpetic neuralgia (pain following shingles).
•Diabetic neuropathy - a nerve disorder that develops in some people with diabetes.
•Phantom limb pain following an amputation.
•Multiple sclerosis.
•Pain following chemotherapy.
•HIV infection.
•Alcoholism.
•Cancer.
•Atypical facial pain.
•Various other uncommon nerve disorders.

Note: you can have nociceptive pain and neuropathic pain at the same time, sometimes caused by the same condition. For example, you may develop nociceptive pain and neuropathic pain from certain cancers.

More about the nature of neuropathic pain

Related to the pain there may also be:
•Allodynia. This means that the pain comes on, or gets worse, with a touch or stimulus that would not normally cause pain. For example, a slight touch on the face may trigger pain if you have trigeminal neuralgia, or the pressure of the bedclothes may trigger pain if you have diabetic neuropathy.
•Hyperalgesia. This means that you get severe pain from a stimulus or touch that would normally cause only slight discomfort. For example, a mild prod on the painful area may cause intense pain.
•Paraesthesia. This means that you get unpleasant or painful feelings even when there is nothing touching you, and no stimulus. For example, you may have painful pins and needles, or electric shock-like sensations.

In addition to the pain itself, the impact that the pain has on your life may be just as important. For example, the pain may lead to disturbed sleep, anxiety and depression.

How common is neuropathic pain?

It is estimated that about 1 in 100 people in the UK has persistent (chronic) neuropathic pain. It is much more common in older people who are more prone to developing the conditions listed above.

What is the treatment for neuropathic pain?

Treatments include:
•Treating the underlying cause - if possible.
•Medicines.
•Physical treatments.
•Psychological treatment.

Treating the underlying cause

If this is possible, it may help to ease the pain. For example, if you have diabetic neuropathy then good control of the diabetes may help to ease the condition. If you have cancer, if this can be treated then this may ease the pain. Note: the severity of the pain often does not correspond with the seriousness of the underlying condition. For example, postherpetic neuralgia (pain after shingles) can cause a severe pain, even though there is no rash or sign of infection remaining.

Medicines used to treat neuropathic pain

Commonly used traditional painkillers

You may have already tried traditional painkillers such as paracetamol or anti-inflammatory painkillers that you can buy from pharmacies. However, these are unlikely to ease neuropathic pain very much in most cases.

Tricyclic antidepressant medicines

An antidepressant medicine in the tricyclic group is a common treatment for neuropathic pain. It is not used here to treat depression. Tricyclic antidepressants ease neuropathic pain separate to their action on depression. It is thought that they work by interfering with the way nerve impulses are transmitted. There are several tricyclic antidepressants, but amitriptyline is the one most commonly used for neuralgic pain. In many cases the pain is stopped, or greatly eased, by amitriptyline. Imipramine and nortriptyline are other tricyclic antidepressants that are sometimes used to treat neuropathic pain.

A tricyclic antidepressant may ease the pain within a few days, but it may take 2-3 weeks. It can take several weeks before you get maximum benefit. Some people give up on their treatment too early. It is best to persevere for at least 4-6 weeks to see how well the antidepressant is working.

Tricyclic antidepressants sometimes cause drowsiness as a side-effect. This often eases in time. To try to avoid drowsiness, a low dose is usually started at first, and then built up gradually if needed. Also, the full daily dose is often taken at night because of the drowsiness side-effect. A dry mouth is another common side-effect. Frequent sips of water may help with a dry mouth. See the leaflet that comes with the medicine packet for a full list of possible side-effects.

Other antidepressant medicines

An antidepressant called duloxetine has also been shown in research trials to be good at easing neuropathic pain. In particular, duloxetine has been found to be a good treatment for diabetic neuropathy and is now often used first-line for this condition. Duloxetine is not classed as a tricyclic antidepressant but as a serotonin and norepinephrine reuptake inhibitor (SNRI). It may be tried for other types of neuropathic pain if a tricyclic antidepressant has not worked so well, or has caused problematic side-effects. The range of possible side-effects caused by duloxetine are different to those caused by tricyclic antidepressants.

Venlafaxine is another SNRI antidepressant medicine that is sometimes used to treat neuropathic pain. Another group of antidepressants are called selective serotonin reuptake inhibitors (SSRIs). There is some evidence to suggest that medicines in this group may help to ease neuropathic pain but more research is needed to confirm this.

Anti-epileptic medicines (anticonvulsants)

An anti-epileptic medicine is an alternative to an antidepressant. For example, gabapentin, pregabalin, sodium valproate, oxcarbazepine and carbamazepine. These medicines are commonly used to treat epilepsy but they have also been found to ease nerve pain. An anti-epileptic medicine can stop nerve impulses causing pains separate to its action on preventing epileptic seizures. As with antidepressants, a low dose is usually started at first and built up gradually, if needed. It may take several weeks for maximum effect as the dose is gradually increased.

Opiate painkillers

Opiate painkillers are the stronger traditional painkillers. For example, codeine, morphine and related drugs. As a general rule, they are not used first-line for neuropathic pain. This is partly because there is a risk of problems of drug dependence, impaired mental functioning and other side-effects with the long-term use of opiates. Also, the medicines listed above tend to work better anyway for neuropathic pain. However, tramadol is often used.

Tramadol is a painkiller that is similar to opiates but has a distinct method of action that is different to other opiate painkillers. A recent research review concluded that tramadol may be a good option for neuropathic pain in certain situations.

Combinations of medicines

For example, sometimes both an antidepressant and an anti-epileptic medicine are taken if either alone does not work very well. Sometimes tramadol is combined with an antidepressant or an anti-epileptic medicine. As they work in different ways, they may compliment each other and have an additive effect on easing pain better than either alone.

Capsaicin cream

This is sometimes used to ease pain if the above medicines do not help, or cannot be used because of problems or side-effects. Capsaicin is thought to work by blocking nerves from sending pain messages. Capsaicin cream is applied 3-4 times a day. It can take up to 10 days for a good pain-relieving effect to occur.

Capsaicin can cause an intense burning feeling when it is applied. In particular, if it is used less than 3-4 times a day, or if it is applied just after taking a hot bath or shower. However, this side-effect tends to ease off with regular use. Capsaicin cream should not be applied to broken or inflamed skin. Wash your hands immediately after applying capsaicin cream.

Other medicines

Some other medicines are sometimes used on the advice of a specialist in a pain clinic. These may be an option if the above medicines do not help. For example, ketamine injections. Ketamine is normally used as an anaesthetic, but at low doses can have a pain-relieving effect. Another example is lidocaine gel. This is applied to skin, with a special patch. It is sometimes used for postherpetic (post-shingles) neuralgia (but note, it needs to be put on to non-irritated or healed skin).

Side-effects and titrating dosages of medicines

For most of the medicines listed above it is common practice to start at a low dose at first. This may be sufficient to ease the pain but often the dose needs to be increased if the effect is not satisfactory. This is usually done gradually and is called titrating the dose. Any increase in dose may be started after a certain number of days or weeks - depending on the medicine. Your doctor will advise as to how and when to increase the dose if required; also, the maximum dose that can be taken for each particular medicine.

The aim is to find the lowest dose required to ease the pain. This is because the lower the dose, the less likely that side-effects will be troublesome. Possible side-effects vary for the different medicines used. A full list of possible side-effects can be found with information in the medicine packet. Some people don't get any side-effects, some people are only mildly troubled by side-effects that are OK to live with, but some people are troubled quite badly by side-effects. Tell your doctor if you develop any troublesome side-effects. A switch to a different medicine may be an option if this occurs.

Physical treatments

Depending on the site and cause of the pain, a specialist in a pain clinic may advise one or more physical treatments. These include: physiotherapy, acupuncture, nerve blocks with injected local anaesthetics and transcutaneous electrical nerve stimulation (TENS) machines.

Psychological treatments

Pain can be made worse by stress, anxiety and depression. Also, the perception (feeling) of pain can vary depending on how we react to our pain and circumstances. Where relevant, treatment for anxiety or depression may help. Also, treatments such as stress management, counselling, cognitive behavioural therapy, and pain management programmes sometimes have a role in helping people with chronic (persistent) neuropathic pain.

http://www.patient.co.uk/health/Neuropathic-Pain.htm

WHY IS EDUCATIONAL ACHIEVEMENT HERITABLE

New research, led by King's College London finds that the high heritability of exam grades reflects many genetically influenced traits such as personality, behaviour problems, and self-efficacy and not just intelligence.

The study, published in the Proceedings of the National Academy of Sciences(PNAS), looked at 13,306 twins at age 16 who were part of the Medical Research Council (MRC) funded UK Twins Early Development Study (TEDS). The twins were assessed on a range of cognitive and non-cognitive measures, and the researchers had access to their GCSE (General Certificate of Secondary Education) scores.

In total, 83 scales were condensed into nine domains: intelligence, self-efficacy (confidence in one's own academic ability), personality, well-being, home environment, school environment, health, parent-reported behaviour problems and child reported behaviour problems.

Identical twins share 100% of their genes, and non-identical twins (just as any other siblings) share 50% of the genes that vary between people. Twin pairs share the same environment (family, schools, teachers etc). By comparing identical and non-identical twins, the researchers were able to estimate the relative contributions of genetic and environmental factors. So, if overall, identical twins are more similar on a particular trait than non-identical twins, the differences between the two groups are due to genetics, rather than environment.

Eva Krapohl, joint first author of the study, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's, says: "Previous work has already established that educational achievement is heritable. In this study, we wanted to find out why that is. What our study shows is that the heritability of educational achievement is much more than just intelligence -- it is the combination of many traits which are all heritable to different extents.

"It is important to point out that heritability does not mean that anything is set in stone. It simply means that children differ in how easy and enjoyable they find learning and that much of these differences are influenced by genetics."

The researchers found that the heritability of GCSE scores was 62%. Individual traits were between 35% and 58% heritable, with intelligence being the most highly heritable. Together, the nine domains accounted for 75% of the heritability of GCSE scores.

Heritability is a population statistic which does not provide any information at an individual level. It describes the extent to which differences between children can be ascribed to DNA differences, on average, in a particular population at a particular time.

Kaili Rimfeld, joint-lead author, also from the IoPPN at King's says: "No policy implications necessarily follow from finding that genetics differences influence educational achievement, because policy depends on values and knowledge. However, our findings support the idea that a more personalized approach to learning may be more successful than a one size fits all approach. Finding that educational achievement is heritable certainly does not mean that teachers, parents or schools aren't important. Education is more than what happens to a child passively; children are active participants in selecting, modifying, and creating their experiences -- much of which is linked to their genetic propensities, known in genetics as genotype-environment correlation."

Why Is Fibromyalgia A Neuropathic Condition

Today's post from consultqd.clevelandclinic.org (see link below) addresses the on-going confusion surrounding fibromyalgia and its relationship with neuropathy. Fibromyalgia is a painful rheumatic condition characterized by muscular or musculoskeletal pain with stiffness and tenderness at specific points on the body. It's often accompanied by extreme tiredness, sleep problems, memory and mood swings. It's a disease that doctors hate because it's so difficult to pin down and so easy to misdiagnose, even to the point of telling patients that it's all between their ears. Because it's associated with rheumatic and muscular problems, there's a fierce debate as to whether it could ever be linked to nerve damage. This article maintains that it's a neurological problem, caused by a damaged nervous system. Strangely, whatever the cause, the treatment follows very much the same lines as that for neuropathy. Whatever the reasons for and causes of, it's a nasty, painful  condition that has patients at the limit of their tolerance because all the pain seems heightened by extreme sensitivity - sounds much like neuropathy to me!!

Why Fibromyalgia Is Neuropathic 

Mar. 8, 2016 / Pain Management / Education
 
Central sensitization is one explanation

The etiology of fibromyalgia is still largely unknown, but it isn’t as controversial as it used to be.

A decade ago, the chronic rheumatic disease was most often attributed to muscle and ligament problems. Some declared it a psychogenic disorder. (Some still do.) More recently, however, studies have linked fibromyalgia with malfunctioning neurotransmitters, neurochemical imbalances and other neuropathic conditions.

“Today, it’s more widely accepted that fibromyalgia is primarily a neurogenic disease,” says Philippe Berenger, MD, a pain management specialist at Cleveland Clinic. “It still doesn’t explain the disease, but it’s a step forward.”

Dr. Berenger bolstered this belief in a presentation at Cleveland Clinic’s 18th Annual Pain Management Symposium in San Diego in March. 

Definitions we can agree on

In 1994, the International Association for the Study of Pain (IASP) defined neuropathic pain as “initiated or caused by a primary lesion or dysfunction of the nervous system.” In 2008, the IASP’s Neuropathic Pain Special Interest Group tweaked the definition to include “disease of the somatosensory nervous system.”

“Fibromyalgia fits these definitions,” says Dr. Berenger. “Although the condition has no anatomically definable lesions, it is marked by altered neurological function in the spinal cord and brain. It can, therefore, be considered a dysfunction of the central inhibitory process of pain control.” 

Fibromyalgia’s link to central sensitization

It’s clear that fibromyalgia has mechanisms and pathways associated with central sensitization, he notes. The condition follows similar pathways as other neuropathic pain syndromes, such as complex regional pain syndrome, interstitial cystitis and irritable bowel syndrome.

“All nerves in fibromyalgia patients are more sensitive than they should be — including the brain and spinal cord,” says Dr. Berenger. “Many patients have difficulty with concentration or have hypersensitivity to light, odors or sounds. Some have additional neuropathic pain syndromes or struggle with autonomic dysfunction, such as vasovagal symptoms.”

Central sensitization has been demonstrated in animals and humans by using various triggers (e.g., mustard oil, heat, hypertonic saline injection) to activate nociceptors in skin, viscera or muscle. Sensitization presents as:
Tactile allodynia
Hyperalgesia
Enhanced pressure and thermal sensitivity
Spreading to neighboring nonstimulated sites and remote regions

Increased excitability of spinal cord neurons can cause a series of events:
Increased duration (spontaneous firing) and a growing area of response
Abnormal neuro-anatomical reorganization (new connections between A-beta, A-delta and C fibers, which spread and involve multiple dermatomes)
Diffuse symptoms — which can outlast the stimuli (long-term potentiation)
Newer evidence supports neurogenic claim

In 2014, researchers discovered through skin biopsy that patients with fibromyalgia had lower epidermal nerve fiber density than patients without fibromyalgia. Small fiber neuropathy, therefore, is likely another contributing factor in fibromyalgia pain — and yet more evidence that the condition has neurogenic roots, notes Dr. Berenger.

What this means for treatment

“Most of the drugs used today to treat fibromyalgia — like antidepressants and antiepileptics — are already focused on neurological targets,” says Dr. Berenger.

However, considering fibromyalgia as a central sensitization disorder opens up a larger array of treatment options, he says. Agents active on the central nervous system include:
Sodium channel blockers
Calcium channel blockers
Serotonin-norepinephrine reuptake inhibitors (SNRI)
NMDA receptor antagonists
Nerve growth factor (NGF) inhibitors

Low-dose naltrexone is another treatment option on the horizon. One 2013 study found that the drug significantly reduced pain and improved mood and general satisfaction in people with fibromyalgia. Other studies have reported similar positive responses to the drug.
“It’s all in the mind”

Saying that fibromyalgia is “all in the mind” isn’t entirely wrong, concludes Dr. Berenger.

“Pain pathways and centers are in the brain. And we can employ techniques like mindfulness and biofeedback to control pain,” he says. “However, it’s more helpful — and accurate — to consider it a neurogenic disorder.”
 
https://consultqd.clevelandclinic.org/2016/03/why-fibromyalgia-is-neuropathic/

Why Do We Take Extra Vitamin B For Neuropathy

Today's post from onlinelibrary.wiley.com (see link below) is an important one for several reasons, not least of which is how it shows readers how complex medical studies are set up and planned. It also questions the role of Vitamin B (in all its forms) in neuropathy treatment. It is true, wherever you look on the internet, you will see articles blithely recommending vitamin B supplementation as an answer to neuropathy symptoms and this has resulted in patients rushing to health food shops and supermarkets to stock up on vitamin B supplements. The problem is that serious studies into vitamin B supplementation are conspicuous by their absence, although occasionally, you'll see a vague warning not to 'overdose'. The most important lesson from all this is that you should only ever supplement an existing deficiency and how will you know you're deficient in vitamin B unless your doctor tests you for it? 90% of the time, patients look at the disease and wrongly conclude that extra vitamin B is the answer, without finding out the levels in their own bodies. Apart from this; which sort of vitamin B are you going to choose...and why. You'll often see vitamin B12 being recommended; or Bi, B2 etc etc, or combinations of B compounds. You get the picture!
This article refers to a study begun in the middle of last year intended 'to assess the effectiveness and safety of vitamin B supplements for the management of pain and nerve damage in people with diabetic peripheral neuropathy.' It also examines the various sorts of vitamin B and explains their purpose. Pretty important don't you think and hopefully it's just the first of many serious studies into supplements and nerve damage. The problem is that when people exhaust all the standard chemical options and the symptoms continue, their next port of call is the supplement industry and its all too voracious marketing campaigns. There's nothing wrong with that, as long as you do your research first and consult your doctor and then stop the supplement if it's having no effect!! Otherwise you're sticking a pin in the ever-growing supplement list and hoping for the best...never the healthiest option...I'm sure you agree.

Vitamin B for treating diabetic peripheral neuropathy
Hanan Khalil, Helen Chambers, Vivian Khalil, Cynthia D Ang

First published: 8 June 2016
Editorial Group: Cochrane Neuromuscular Group
DOI: 10.1002/14651858.CD012237View/save citation
Cited by: 0 articles

Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effectiveness and safety of vitamin B supplements for the management of pain and nerve damage in people with diabetic peripheral neuropathy.

Background
Description of the condition

Peripheral neuropathy is the most common risk factor for foot ulcers in people with diabetes (Duby 2004). More than 80% of all non-traumatic amputations in diabetic patients are the result of foot ulcers (Singh 2005). In 2010, the estimated world prevalence of diabetes was 285 million, a figure expected to rise to 439 million by 2030 (Shaw 2010). Diabetic peripheral neuropathy (DPN) is then expected to affect around 236 million, constituting a major cause of mortality and morbidity, with a significant associated financial cost (Tesfaye 2012). The annual cost of DPN in the United States was estimated to be USD 10.9 billion in 2010 (Gordois 2003; Zhang 2010).

Diabetic neuropathy can be divided into four broad patterns, depending upon which nerves are affected: DPN, proximal neuropathy, autonomic neuropathy, and focal neuropathies (American Diabetes Association 2014; Boulton 2004). Diabetic neuropathy affects long fibres first, including the feet and distal legs. Proximal neuropathy is often asymmetric and may involve the thighs, hips, or buttocks. Autonomic neuropathy can cause dysfunction of the gastrointestinal system, blood vessels, and urinary system, and sexual dysfunction. Focal neuropathies often occur at common sites of nerve compression and affect nerves such as the ulnar and median nerves in the arm, the peroneal nerve in the leg, nerves of the thoracic and lumbar regions, and specific cranial nerves (Boulton 2004).

The American Diabetes Association has defined DPN as “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (American Diabetes Association 2014). Symptoms of DPN include numbness or reduced ability to feel pain, muscle weakness, difficulty walking, and serious foot problems (Boulton 1998; Hughes 2002; Huskisson 1974).

No gold standard for diagnosing DPN exists; the history and physical examination are key, as the diagnosis remains clinical (American Diabetes Association 2014). Supportive semi-quantitative testing, such as monofilament testing (using von Frey hairs), nerve conduction studies, electromyography, and quantitative sensory testing, can also be used (Bril 2013). Exclusion of non-diabetic causes should also be undertaken, again through history, examination, and the judicious use of investigations such as serum vitamin B₁₂, thyroid function tests, blood urea nitrogen, and serum creatinine (Perkins 2001).

Early diagnosis and management of DPN are crucial for the prevention of amputations, foot ulcers, and other injuries. Successful diagnosis and management require early screening for high-risk individuals (American Diabetes Association 2014; Khalil 2013a).

Treatment of DPN is multifaceted: components include stable glucose control; regular physical check-ups including foot care; patient education; and specialist care when needed (Callaghan 2012). Pain management includes the use of medications such as, for example, pregabalin, sodium valproate, dextromethorphan, tramadol, opioids and, in some cases, topical capsaicin and lidocaine (Khalil 2013b).

Description of the intervention

The B vitamins comprise eight water-soluble compounds that have essential roles in cell metabolism: vitamin B₁ (thiamine), vitamin B₂ (riboflavin), vitamin B₃ (niacin, niacinamide, or nicotinic acid), vitamin B₅ (pantothenic acid), vitamin B₆ (pyridoxine, pyridoxal, pyridoxamine, or pyridoxine hydrochloride), vitamin B₇ (biotin), vitamin B₉ (folic acid) and vitamin B₁₂ (hydroxycobalamins, cobalamins). Each one of these components has a different physical and chemical structure and completes an essential function in the human body (Chaney 1992; Olson 1996).

Vitamins B₁, B₂, B₃, and biotin are involved in energy production; vitamin B₆ is required for amino acid metabolism. Thiamine is converted to thiamine pyrophosphate which has a role in carbohydrate metabolism. Thiamine pyrophosphate also plays a role in the transmission of nerve impulses. Riboflavin is converted into flavin mononucleotide and flavin adenine dinucleotide that serve as coenzymes for respiratory flavoproteins. The active forms of nicotinic acid are coenzymes for proteins that catalyse oxidation-reduction reactions in tissue respiration (Chaney 1992; van Boxtel 2001).

Vitamin B₆ is converted to pyridoxal phosphate and is involved in the metabolic transformations of amino acids and in the metabolism of sulphur-containing and hydroxyl-amino acids. Pyridoxal phosphate is required for the synthesis of sphingolipids for myelin formation. Vitamin B₁₂ has several congeners: cyanocobalamin, hydroxocobalamin, methylcobalamin, and 5’-deoxyadenosylcobalamin. Vitamin B₁₂ and folic acid facilitate essential steps in cell division (Chaney 1992; Hillman 1996).

Common vitamin B deficiency features include peripheral neuropathy, depression, mental confusion, lack of motor co-ordination, and malaise. Vitamin B deficiencies cause various diseases in humans such as beriberi (thiamine deficiency), pellagra (nicotinamide deficiency), megaloblastic anaemia (folic acid deficiency), and pernicious anaemia (cobalamin deficiency) (De-Regil 2010; Lassi 2013; Rodríguez-Martín 2001). The therapeutic doses for the various forms of vitamin B complex range widely, from 3 μg/day for vitamin B₁₂ to 18 mg/day for vitamin B₃ in adult males (Chaney 1992; Hillman 1996).

How the intervention might work

The mechanisms by which neuropathic pain develops in diabetes are unclear; mechanisms postulated include alteration in peripheral blood flow, increased vascularity, oxidative stress, and autonomic dysfunction (Edwards 2008; Tesfaye 2011). Overall, there is a paucity of evidence on the role of B vitamins in diabetes. Several studies found lower than normal levels of thiamine in people with diabetes, thought to be due to high renal clearance of thiamine and increased albuminuria in diabetes (Thornalley 2005). Moreover, vitamin B₁₂ deficiency has also been observed in patients with diabetes, partially explained by metformin-induced vitamin B₁₂ deficiency, particularly among people on high doses of metformin (Kibirige 2013). Mecobalamin is a derivative of vitamin B₁₂ involved in processes essential to myelin repair (Sun 2005).

Why it is important to do this review

Untreated DPN is not only associated with a significant cost to the health care system, but has a serious impact on a person's quality of life and general health. If left untreated, serious complications such as loss of function and amputations can occur. To date, evidence on the effectiveness and safety of vitamin B supplements for the treatment of DPN as an additional or alternative option to current treatments have not been fully evaluated. This review will address these issues (Rolim 2009).

Objectives

To assess the effectiveness and safety of vitamin B supplements for the management of pain and nerve damage in people with diabetic peripheral neuropathy.
Methods
Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) and quasi-RCTs (studies that allocate participants to groups by methods that are partially systematic, for example by allocation, case record number or date of birth). We will apply no language limitations. We will include studies completed but not fully reported to reduce the risk of publication bias.

Types of participants

We will include trials of adults, children, or both, with a diagnosis of DPN based on symptoms, abnormal physiological test results, or both. For the purpose of this review, we will use the definitions of diabetes and DPN set by the American Diabetes Association (American Diabetes Association 2014). We will exclude participants with other types of neuropathy. We will exclude people who are vitamin B depleted and taking supplements for replenishment. Participants should not have taken B vitamins in the six months before the start of treatment.

Types of interventions

We will consider trials for inclusion where the intervention is any dose and type of vitamin B supplement (thiamine (B₁), riboflavin (B₂), nicotinic acid (B₃), pyridoxine (B₆), and methylcobalamin, cyanocobalamin, hydroxycobalamin, methylcobalamin, or 5’-deoxyadenosylcobalamin (B₁₂), given by any route, singly or in combination as vitamin B complexes, in comparison to placebo, no treatment, or any comparators for a minimum period of 12 weeks. We will consider trials of vitamin B complexes so long as details of the components are provided.

We will exclude studies using supplements in combination with other vitamins or drugs unless the other vitamins or drugs are administered at the same dose in both intervention and control groups.
Types of outcome measures

Primary outcomes

For painful neuropathy: short-term (three months or less) change in pain intensity, measured as the number of participants with more than a 30% improvement in pain intensity.

For non-painful neuropathy: short-term change in impairment measured by a validated scale, e.g. neuropathy impairment score (NIS) (Dyck 2005).

Secondary outcomes

Long-term (after more than three months) change in pain intensity, measured as the number of participants with more than a 30% improvement in pain.

Long-term (after more than three months) change in impairment measured by a validated scale as for the primary outcome.

3. Change in quality of life measured by a validated scale (e.g. Short-Form 36 Health Survey (SF-36)).

4. Adverse events, reported as all adverse events, adverse events which led to cessation of treatment, and serious adverse events which were life-threatening, fatal, or required or prolonged hospitalisation.
Search methods for identification of studies

Electronic searches

We will identify trials from the Cochrane Neuromuscular Specialized Register, which is maintained by the Information Specialist for the Group. The Information Specialist will search the Cochrane Central Register of Controlled Trials (CENTRAL) (current issue in The Cochrane Library), MEDLINE (January 1966 to current), EMBASE (January 1980 to current), and CINAHL Plus (January 1937 to current). We will adapt the draft MEDLINE strategy in Appendix 1 to search the other databases.

We will also search the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/). We will search all databases from inception to present.

Searching other resources

We will search reference lists of all primary studies and review articles to identify additional references. We will search relevant manufacturers' websites for trial information. We will search for errata or retractions of included trials.
Data collection and analysis

Selection of studies

Three review authors (HK, CA, and VK) will independently screen titles and abstracts of references from the literature searches and code them as either 'retrieve' (eligible or potentially eligible/unclear) or 'do not retrieve'. We will retrieve the full-text study reports or publications and three review authors (HK, CA and VK) will independently screen the full text and identify studies for inclusion. The review authors will identify and record reasons for exclusion of ineligible studies. We will resolve any disagreement through discussion or, if required, we will consult a third person (HC). We will identify and exclude duplicates and collate multiple reports of the same study so that each study rather than each report is the unit of interest in the review. We will record the selection process in sufficient detail to complete a PRISMA flow diagram and 'Characteristics of excluded studies' table. The review authors will not assess trials in which they are investigators.

Data extraction and management

We will use a data extraction form, which has been piloted on at least one study in the review, for study characteristics and outcome data. Two review authors (VK and HK) will extract study characteristics from included studies.
 We will extract the following study characteristics.

Methods: study design, total duration of study, details of any 'run in' period, number of study centres and location, study setting, withdrawals, and date of study.

Participants: N, mean age, age range, gender, severity of condition, diagnostic criteria, baseline characteristics, inclusion criteria, and exclusion criteria.

Interventions: intervention, comparison, concomitant medications, and excluded medications.

Outcomes: primary and secondary outcomes specified and collected, and time points reported.

Notes: funding for trial, and notable conflicts of interest of trial authors.

Two review authors (CA and HK) will independently extract outcome data from included studies. We will note in the 'Characteristics of included studies' table if the trial report did not provide usable outcome data. We will resolve disagreements by consensus or by involving a third person (VK). One review author (HK) will transfer data into Review Manager (RevMan 2014). A second author will check the outcome data entries. A second review author (CA) will spot-check study characteristics for accuracy against the trial report.
Assessment of risk of bias in included studies

Two review authors (HK and CA) will independently assess risk of bias in each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve any disagreements by discussion or by involving another author (VK). We will assess the risk of bias according to the following domains.

Random sequence generation.

Allocation concealment.

Blinding of participants and personnel.

Blinding of outcome assessment.

Incomplete outcome data.

Selective outcome reporting.

Other bias.

We will grade each potential source of bias as high, low or unclear and provide a quote from the study report together with a justification for our judgment in the 'Risk of bias' table. We will summarise the 'Risk of bias' judgments across the included studies for each of the domains listed. We will consider blinding separately for different key outcomes (e.g. for unblinded outcome assessment, risk of bias for all-cause mortality may be very different than for a patient-reported pain scale). Where information on risk of bias relates to unpublished data or correspondence with a trialist, we will note this in the 'Risk of bias' table.

When considering treatment effects, we will take into account the risk of bias for the studies that contribute to that outcome.
Assesment of bias in conducting the systematic review

We will conduct the review according to this published protocol and report any deviations from it in the 'Differences between protocol and review' section of the Cochrane review.

Measures of treatment effect

We will analyse dichotomous data as risk ratios and continuous data as mean difference, or standardised mean difference for results across studies with outcomes that are conceptually the same but measured in different ways. We will enter data presented as a scale with a consistent direction of effect. We will combine all the data for the outcomes measures provided that the intervention lasted for 12 weeks or more irrespective of the differences in times at which outcomes are calculated between trials.

We will undertake meta-analyses only where this is meaningful, i.e. if the treatments, participants and the underlying clinical question are similar enough for pooling to make sense. We will narratively describe skewed data reported as medians and interquartile ranges.

Unit of analysis issues

The unit of analysis is based on the individual participant (unit to be randomised for interventions to be compared), that is the number of observations in the analysis should match the number of individuals randomised (Higgins 2003).

Where multiple trial arms are reported in a single trial, we will include only the arms relevant to this review. If two or more comparisons (e.g. drug A versus drug B versus placebo) are suitable for inclusion in the same meta-analysis we will combine the relevant intervention groups together or relevant control groups together, or both, as appropriate to create a single pair-wise comparison as recommended in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If this is not possible we will follow alternative methods described in the same chapter.

We will consider only first period data from eligible randomised cross-over studies.

Dealing with missing data

We will report drop-out rates in the 'Characteristics of included studies' table and we will use intention-to-treat analysis (Higgins 2011). We plan to contact trial authors for missing data.

Assessment of heterogeneity

We will consider clinical heterogeneity before making a decision whether to pool studies. We will only perform meta-analysis if participants, interventions and comparisons are sufficiently similar. We will use the I² statistic to measure statistical heterogeneity among the trials in each analysis. If we identify substantial unexplained heterogeneity we will report it and explore possible causes by prespecified subgroup analysis. We will use the following thresholds as a rough guide for interpretation of I², as described in Higgins 2011.

0% to 40%: might not be important.

30% to 60%: may represent moderate heterogeneity.

50% to 90%: may represent substantial heterogeneity.

75% to 100%: considerable heterogeneity.
Assessment of reporting biases

If we are able to pool more than 10 trials, we will create and examine a funnel plot to explore possible small study biases.

Data synthesis

We will use a fixed-effect model in meta-analysis and if heterogeneity is present, compare these results with a those of a random-effects analysis. If the review includes more than one comparison that cannot be included in a single analysis, we will report results for each comparison separately. If the studies have significant heterogeneity and cannot be combined, we will report findings in a narrative form.

We will consider studies of vitamin B complexes as one supplement for the purposes of meta-analysis, taking into account the potential heterogeneity and indirectness of evidence from such analyses when we assess the quality of the evidence.

'Summary of findings' tables

We will create 'Summary of findings' tables using the primary and secondary outcomes. We will use the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence (studies that contribute data for the prespecified outcomes). We will use methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) using GRADEproGDT software (GRADEpro 2014). We will justify decisions to downgrade or upgrade the quality of the evidence using footnotes and where necessary we will make comments to aid readers' understanding of the review.
Subgroup analysis and investigation of heterogeneity

We plan to carry out the following subgroup analyses.


Types of vitamin B supplement.


Children under 18 and adults.

We will use the primary outcome in subgroup analyses in Review Manager (RevMan 2014).
Sensitivity analysis

We plan to perform the following sensitivity analyses.

Repeat the analysis excluding studies at high risk of bias (from randomisation or blinding of participants).

If there is one or more very large study, repeat the analysis excluding them to determine how much they dominate the results.

Repeat the analysis using a random-effects model if heterogeneity is present.
Reaching conclusions

We will base our conclusions only on findings from the quantitative or narrative synthesis of included studies. Our implications for research will suggest priorities for future research and outline what the remaining uncertainties are in the area.
Acknowledgements

The authors would like to acknowledge the editorial support from Cochrane Neuromuscular and the Information Specialist (Angela Gunn) who developed the search strategy in collaboration with the review authors.

Some sections of the review are based on Ang 2008 and on a protocol template originally developed by Cochrane Airways and adapted by Cochrane Neuromuscular.

This project was supported by the National Institute for Health Research (NIHR) via Cochrane Infrastructure funding to Cochrane Neuromuscular. The views and opinions expressed herein are those of the review authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service, or the Department of Health. Cochrane Neuromuscular is also supported by the MRC Centre for Neuromuscular Diseases.

Appendices
Appendix 1. DRAFT MEDLINE (OvidSP) search strategy

Database: Ovid MEDLINE(R) <1946 2014="" 4="" october="" to="" week="">
Search Strategy:
--------------------------------------------------------------------------------
1 randomized controlled trial.pt. (397786)
2 controlled clinical trial.pt. (90503)
3 randomized.ab. (293092)
4 placebo.ab. (154196)
5 drug therapy.fs. (1777958)
6 randomly.ab. (205733)
7 trial.ab. (305213)
8 groups.ab. (1307610)
9 or/1-8 (3350308)
10 exp animals/ not humans.sh. (4082107)
11 9 not 10 (2854354)
12 exp Diabetes Mellitus/ (328635)
13 diabet$.mp. (462274)
14 12 or 13 (463642)
15 exp Peripheral Nervous System Diseases/ (119617)
16 15 or (neuropath$ or polyneuropath$).mp. (182081)
17 14 and 16 (20728)
18 Diabetic Neuropathies/ (12459)
19 17 or 18 (20728)
20 exp Vitamin B Complex/tu [Therapeutic Use] (23726)
21 (aminonicotinamide or cobamide$1 or cyanocobalamin or flavin mononucleutide or flavin adenine dinucleotide or fursultiamin or hydroxycobalamin or hydroxocobalamine).mp. (7678)
22 (methylcobalamin or nicorandil or nicotinic acid or nikethamide or pyridoxal or pyridoxamine or pyridoxine or riboflavin or thiamine or vitamin b complex).mp. (54422)
23 or/20-22 (74266)
24 11 and 19 and 23 (203)
25 remove duplicates from 24 (199)
Contributions of authors
HK drafted the protocol. All the other authors provided feedback on it.
Declarations of interest
None known.
Sources of support
Internal sources

None, Other.
External sources

No sources of support supplied

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012237/full

Why Are You Feeling So Much Leg And Foot Pain

Today's post from huffingtonpost.com (see link below) looks at the various possible reasons for having leg pain. As neuropathy cases increase and more and more people become aware of what it is, it's important to realise that not all leg and foot pains may be the result of nerve damage. There are other better-known causes of leg and foot pain and it's important to exclude those before coming to any conclusions regarding neuropathy. This article is a useful one and provides lots of information to help you decide what may be causing your discomfort. Your doctor may tell you otherwise in the end but at least you'll have some understanding of the possible diagnoses and a basis for discussion with your doctor.

This May Be Causing Your Leg Pain And Numbness
Leg discomfort can knock you off your feet and it should never be ignored.
Winnie Yu Next Avenue 2017

Aching calves, burning legs, numbness in the feet — pain and discomfort in the lower extremities is a common complaint that sends many of us to our doctors seeking relief.

But unless the cause is something obvious, like a fall, pinpointing the source may require some medical detective work. Trying to tough it out, though, will not get you any closer to the answers.

“Leg pain that comes on acutely with a bang, is severe and doesn’t resolve within minutes probably needs to be seen right away,” as it could be a sign of a more serious condition, says Dr. Benjamin Wedro, a clinical professor of medicine at the University of Wisconsin and an emergency physician at Gundersen Medical Center in Lacrosse, Wis. “There’s no trophy for suffering.”

Here are some of the potential causes of leg and foot pain:

Blood Vessel Distress

Pain that occurs when walking or exercising may be the result of claudication or decreased blood supply to the legs. This condition is most often a symptom of peripheral arterial disease, or PAD, a narrowing of the arteries that deliver blood to your limbs, typically caused by the buildup of plaque or fatty deposits. Smoking, high cholesterol, high blood pressure and obesity are major risk factors for PAD.

“The leg pain from PAD tends to occur when you’re active,” says John Fesperman, a family nurse practitioner at Duke Primary Care in North Carolina. “When you’re active, muscles need more blood. The lack of adequate blood triggers pain, which is known as intermittent claudication. Once you stop moving, the pain usually disappears.”

Deep vein thrombosis, or DVT, a blood clot in a deep vein that develops after extended periods of inactivity, can also cause major leg pain. Long flights or car rides make it difficult for the leg to return blood back to the heart. If that blood return slows or stops, it can create a clot within the vein. And if part of a clot breaks off and travels to the lungs, it can cause a pulmonary embolism, a serious and potentially fatal blockage of blood flow to the lungs.

DVT usually occurs in only one leg, Wedro says, causing it to swell and turn a bluish hue. “The onset of pain is gradual and tends to occur over a course of hours,” he says.

Peripheral Neuropathy

In some people, leg and foot (and sometimes arm and hand) pain can be the result of neuropathy, a disorder of the peripheral motor, sensory and autonomic nerves that connect the spinal cord to our muscles, skin and internal organs. Neuropathy can cause numbness, tingling and a heavy sensation. “It usually starts in the feet and may cause a burning sensation in the legs,” Fesperman says. In some cases, people may lose their ability to feel sensation in their legs, which can put them at risk for injury and infection.

Neuropathy can be brought on by many factors, including infection, toxins and the effects of alcoholism, but diabetes is the most common cause. According to the Neuropathy Association, approximately 60 to 70 percent of people with diabetes will at some point develop peripheral neuropathy. It can also affect people who have pre-diabetes and may not be experiencing any other diabetic symptoms.

Electrolyte Imbalance

Healthy muscle function depends on nerves being supported by a well-balanced mix of electrolytes — minerals like sodium, potassium, calcium and magnesium that have an electric charge. Electrolytes transmit signals that support nerve, heart and muscle function, and affect the amount of water in your body as well.

But certain medications; dehydration; and conditions like diarrhea and kidney disease can alter your electrolyte balance. When electrolyte levels become too low, it can cause leg pain. For example, when sodium, which attracts water to cells, is depleted, cells straining to compensate for the lack of fluid can bring on painful cramps.

Diuretics prescribed to control blood pressure are the most common culprits, Fesperman says, because they can deplete electrolytes in the blood. “Potassium and calcium mediate muscle contraction,” he says. “An imbalance in either or both can cause muscle cramping.”

By reducing blood flow, dehydration can cause electrolyte imbalance, and cramps, as well. Likewise, if you drink too much water, you can flush out too many electrolytes.

Back Problems

Conditions that affect your back often lead to pain in the legs as well. Spinal stenosis, in which the spinal canal gradually narrows, pressuring the nerves, usually affects people over 50 and can be caused by arthritis, scoliosis or spinal injury. The pressure can impinge on nerve roots as they leave the spinal cord to form the sciatic nerve, the body’s largest. The irritated nerves can cause significant pain.

Sciatica, a painful inflammation of the sciatic nerve, is typically experienced on one side of the body, and can travel from your lower back down your leg to your feet or even toes. Sciatica is difficult to diagnose and sometimes goes away on its own. It can be brought on by spinal stenosis.

“Sciatic and spinal conditions may come on gradually over time but may also have an acute onset,” Wedro says. “Over time, what had been tolerable becomes an acute issue. Sciatic nerve inflammation caused by changes in the back, such as arthritis, muscle spasm or injury, may radiate into the buttocks and down the leg.”

If the leg pain is accompanied by the loss of bladder or bowel control or numbness near the anus or vagina, seek emergency care immediately. You may have cauda equina syndrome, a rare disorder affecting the nerve roots at the lower end of the spine. Without immediate treatment, the spinal cord can shut down and you may develop permanent paralysis.

Arthritis

There are many types of arthritis. Osteoarthritis, the most common form, breaks down the cartilage in your joints, causing a buildup of painful bone spurs, cartilage loss, inflammation or soreness. Rheumatoid arthritis, an autoimmune disease, attacks the lining of the joints, also causing inflammation and pain.


Although arthritis is a joint disease, the pain it causes can be felt in the surrounding leg and foot muscles. “Any joint under stress can cause pain,” Wedro says. “The pain is within the joints. But the muscles around it try to protect it and you can go into spasms and get secondary muscle pain.”

Getting Treatment for Leg Pain

The appropriate treatment for leg pain depends on the underlying cause. Diabetics may need to improve their blood glucose control to prevent diabetic neuropathy, while arthritis sufferers may need medication or surgery.

“All treatments aim for long-term control of symptoms,” Wedro says. “There may not be one cocktail that works for everybody. It all depends on what has caused the leg pain. It will be trial and error for you and your doctor to find the treatment that works.”

The bottom line? Take all leg and foot discomfort seriously. “Pain means part of the body isn’t working right,” Wedro says. “The problem might be a disaster that is life- or limb-threatening, or it may be an inconvenience that might resolve with a little time and care. But if you have pain, see your doctor. Never dismiss it.”

http://www.huffingtonpost.com/entry/this-is-what-may-be-causing-your-leg-pain-and-numbness_us_57fd2a14e4b0b6a43035e269

Youve Got Neuropathy But Why Do The Tests Show Nothing

Today's post from neuropathyjournal.org (see link below) is another well-written post by Lt.Col. Richardson, in which he quite rightly takes doctors and neurologists to task for their often summary dismissal of neuropathy patients as 'idiopathic' and thus 'unproved'. What do you feel when a doctor says 'the tests all came back normal'? The implication is that either you're exaggerating, or lying, or somehow wasting their time, especially if you're then sent home, or pointed somewhere else on the medical spectrum. These are neurologists and other qualified medical professionals who often say this and they should know better. A patient's story and symptoms should be enough to establish nerve damage; the tests can only point to the extent of the damage and hint at the cause but should never be regarded as a definitive diagnosis upon which further treatment depends. As the Lt. Colonel points out in his ten facts you should be aware of; there is still a need for much greater research and much better education for the medical professionals themselves - insurances, jobs, benefits and people's lives depend on it! Worth a read!

I Have Neuropathy – So Why Are My Tests Normal?
By LtCol Eugene B Richardson, USA (Retired) BA, MDiv, EdM, 

Being a patient with CIDP/Autonomic PN for over 45 years due to exposure to Agent Orange in Vietnam, this is a subject with which I have a lot of hard earned experience.

So, let me be clear. The over two hundred doctors I saw for my symptoms from 1969 to 2003, including those noted below are highly trained medical experts. So what was the problem with getting an accurate diagnosis and treatment during those decades?

For over three decades, upon complaining of symptoms since 1969, I was told by the doctors, “All tests are normal”. They implied, and I assumed this meant, I did not have anything wrong or did not have neuropathy.

One neurologist in 1979 did hedge his opinion stating “probably not neurological.” The word ‘probably’ without providing a medical opinion as to what may be wrong was not very helpful. So what was the problem?

In 1983, fifteen years after the horrific symptoms began; I became upset when the doctor said to me, “Why do you want something to be wrong?” Now I knew something was wrong and I wanted it fixed? Of course the doctor meant it was a mental problem and I concluded at the time I surely must be crazy. So what was the problem?

In 1999 after a doctor finally told me I had idiopathic peripheral neuropathy, I was sent to an expert neurologist who tested my reflexes and with compression on the leg he managed to get reflexes. Based on his special reflex test, he dismissed the diagnosis of idiopathic peripheral neuropathy, stating “patient has reflexes upon compression – patient is claiming to have something he does not have”, almost destroying what remained of my mental stability!

Not until years later did I understand that even the diagnosis that included the word ‘idiopathic’ was part of the problem involving the lack of clinical medical training in understanding the tests and what they do mean or do not mean or measure!

A neurologist in 2005 seven days after receiving gamma globulin for my diagnosed condition and at the peak of the infusions positive documented effect on my neurological illness, dismissed the diagnosis stating, “I cannot find any reasons for patients symptoms.”

Today, we have come a long way in the increase in information on Neuropathy, the increased understanding of neuropathic pain, and the skill of physicians to interpret the tests that are available. But it still takes a highly trained neuromuscular neurologist with special training in this area to diagnose and treat neuropathy. To understand the complexity of getting a diagnosis, perhaps read what Waden Emery III, MD Clinical Neurologist states about What is Neuropathy?

So the question I asked was – if you have neuropathy – so why are tests normal? Thank heavens that because of the hard work of many, we can answer that question clearly.

Here are TEN CURRENT FACTS every neuropathy patient must know!

FIRST, there are no objective tests for diagnosis of neuropathy and early in the illness; the doctor may have only your medical history and a subjective description of your symptoms. The current tests measure any damage to the large or small fibers, axon or myelin, and whether it is a single neuropathy or a polyneuropathy (affecting many nerves).

SECOND, neurology does not have the tools to diagnose peripheral neuropathy objectively, UNTIL damage can be measured or its affects are seen on the body (i.e. deformed feet in CMT, GBS patient can’t breathe, MMN patient can’t move an arm, or multiple issues with digestion, urination, sweating, etc.- See Dr. Norman Latov’s book for definition of acronyms.)

THIRD, peripheral neuropathy is diagnosed by ruling out possible causes of your symptoms. The tests done only look for that cause, not whether you have neuropathy or not, thus many tests are normal! Yet the type of neuropathy, which can often point toward a cause can be determined by these tests and the neurologist must indicate the type, not idiopathic which is not helpful. The failure to find a cause from the tests conducted rules out that cause, not your neuropathy.

FOURTH, testing is done to determine any measurable damage to the nerve or covering of the nerve and perhaps point to the possible type of neuropathy, not whether you have peripheral neuropathy or not.

In 2015 more doctors are understanding the need for the skin biopsy if the EMG or Nerve Conduct Tests do not show damage to the large fibers. More doctors are understanding the value of the spinal tap in diagnosis of an immune mediated neuropathy or the value of the genetic testing that will provide the patient with important affirmation!

FIFTH, most objective tests only determine the extent of damage to the peripheral nervous system, but if you have no or little damage this does not rule out a peripheral neuropathy, as it many chronic progressive neuropathies it can take years before damage can be measured.

SIXTH, the medical literature, including statements by Dr. Norman Latov of Columbia University, note that in Peripheral Neuropathy, reflexes may be absent or diminished, but not always, so alone this is not a standard for diagnosis of or dismissal of neuropathy.

SEVENTH, symptoms including painful skin on touching or sensations of pin prick, or sensitivity to hot or cold, as well as other symptoms, remit and relapse in patients with peripheral neuropathy and thus are only reliable for diagnosis when correlated with ALL available information including the patient’s medical history.

EIGHTH, treatment by gamma globulin does reduce the symptoms of immune-mediated neuropathies and this positive response confirms the diagnosis, thus a physician should not dismiss an existing diagnosis based on the absence of the symptoms following the infusion of gamma globulin or other effective treatments.

NINTH, as noted by Russell Chin, MD, Neurologist in New York City, we need better clinical training for doctors including neurologists both in the medical schools and updated clinical training for practicing physicians. The clinical training of all neurologists and physicals working with neuropathy patients must be a top priority for medical and neuropathy organizations.

TENTH, we desperately need MORE neuropathy research seeking better diagnostic tools for doctors, more treatment options, and improved approaches to treatment of chronic neuropathic pain.

Pam Shlemon, President of the Foundation for Peripheral Neuropathy is working with researchers to deal with the problem that very few research projects even make it to phase 3 trials and the question is why? Hopefully, her team will discover some answers and provide better direction for research.

An early diagnosis of the cause of a neuropathy and approaches to treatment are critical for many patients to prevent serious disability or worse from damage to the peripheral nervous system.

One could call these the TEN COMMANDMENTS for diagnosis of peripheral neuropathy!

https://neuropathyjournal.org/have-neuropathy-so-why-are-tests-normal/

How And Why Nerve Cells Die

Today's interesting post from medicalxpress.com (see link below) looks at the processes involved in nerve death in cases of neuropathy and asks the question whether new discoveries will eventually lead to better therapies in the future. Looking at neuropathy in this detail can often be confusing for casual readers but this article explains the subject in an easily understood manner. Worth a read. (Checking the nerve cell image next to the title may help you understand some of the terminology.)

Major pathway identified in nerve cell death offers hope for therapies 
Provided by Washington University School of Medicine April 23, 2015
 
Axon degeneration (top), caused by nerve injury or disease, depletes the energy supply within axons, shutting down communication between nerve cells. Washington University scientists blocked axon degeneration by supplementing neurons with a …more

New research highlights how nerves - whether harmed by disease or traumatic injury - start to die, a discovery that unveils novel targets for developing drugs to slow or halt peripheral neuropathies and devastating neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS).

Peripheral neuropathy damages nerves in the body's extremities and can cause unrelenting pain, stinging, burning, itching and sensitivity to touch. The condition is commonly associated with diabetes or develops as a side effect of chemotherapy.

The research, by scientists at Washington University School of Medicine in St. Louis, is reported online April 23 in the journal Science.

Nerve cells talk to each other by transmitting signals along communication cables called axons. Such signals underlie vital activities, such as thinking and memory, movement and language.

As part of the study, the researchers showed they could prevent axons from dying, a finding that suggests therapies could be developed to counteract the withering away of nerve axons.

"We have uncovered new details that let us piece together a major pathway involved in axon degeneration," said senior author Jeffrey Milbrandt, MD, PhD, the James S. McDonnell Professor and head of the Department of Genetics. "This is an important step forward and helps to identify new therapeutic targets. That we were able to block axon degeneration in the lab also gives us hope that drugs could be developed to treat patients suffering from a variety of neurological conditions."

A common thread among many neurological disorders and traumatic nerve injuries is the degeneration of axons, which interrupts nerve signaling and prevents nerves from communicating with one another. Axon degeneration is thought to be an initiating event in many of these disorders. In fact, an unhealthy axon is known to trigger its own death, and researchers are keenly interested in understanding how this happens.

Working in cell cultures, fruit flies and mice, Milbrandt and co-author Aaron DiAntonio, MD, PhD, the Alan A. and Edith L. Wolff Professor of Developmental Biology, and their colleagues showed that a protein already known to be involved in axon degeneration, acts like a switch to trigger axon degeneration after an injury.
M.D./Ph.D. student Josiah Gerdts (left) and Jeffrey Milbrandt, M.D., Ph.D., head of the Department of Genetics at Washington University School of Medicine, have identified a major pathway in the death of nerve axons, which carry messages …more

Moreover, they found that this protein, once unleashed, causes a rapid decline in the energy supply within axons. Within minutes after the protein - called SARM1 - is activated in neurons, a massive loss of nicotinamide adenine dinucleotide (NAD), a chemical central to a cell's energy production, occurs within the axon.

"When a nerve is diseased or injured, SARM1 becomes more active, initiating a series of events that quickly causes an energetic catastrophe within the axon, and the axon undergoes self-destruction," said first author Josiah Gerdts, an MD/PhD student in Milbrandt's laboratory.

Working in neurons in which SARM1 was activated, the researchers showed they could completely block axon degeneration and neuron cell death by supplementing the cells with a precursor to NAD, a chemical called nicotinamide riboside. The neurons were able to use nicotinamide riboside to keep the axons energized and healthy.

Nicotinamide riboside has been linked in animal studies to good health and longevity, but its benefits have not been shown in people. The researchers said much more research is needed to know whether the chemical could slow or halt axon degeneration in the body.

"We are encouraged by the findings and think that identifying a class of drugs that block SARM1 activity has therapeutic potential in neurological disorders," Milbrandt said. "The molecular details this pathway provides give us a number of therapeutic avenues to attack."

Explore further: Study detailing axonal death pathway may provide drug targets for neurodegenerative diseases

More information: Gerdts J, Brace EJ, Sasaki Y, DiAntonio A and Milbrandt J. SARM1 activation triggers axon degeneration locally via NAD+ destruction. Science. April 24, 2015. www.sciencemag.org/lookup/doi/… 1126/science.1258366

Journal reference: Science

http://medicalxpress.com/news/2015-04-major-pathway-nerve-cell-death.html

Tingling And Burning Feet Why

Today's post from livestrong.com (see link below) will be self-evident for those neuropathy sufferers who've lived with the problem for some time but what happens when you experience these feelings for the first time? You can be bewildered as to why this is happening to you and you may never have heard the word 'neuropathy' let alone have an understanding of what it means. This article will fill in some of the gaps for you and give you a sound basis for your first visit to a doctor or specialist. Worth a read for nerve damage 'newbies'

Causes of Burning and Tingling Feet 
by NIYA JONES Last Updated: Jun 27, 2016

Most people don't think much about their feet until they hurt or give you trouble. Burning and tingling in the feet usually signals nerve irritation that may be due to injury, infection or other medical disorders. Chronic nerve damage, known as peripheral neuropathy, commonly causes a pins-and-needles sensation in the feet that can make it tough to walk. Depending on the cause, potential complications of peripheral neuropathy include foot ulcers, muscle loss and paralysis, in rare cases.

Metabolic Disorders

A host of metabolic conditions can lead to burning and tingling in the feet. Diabetes is among the most frequent causes. People with diabetes who have peripheral neuropathy are prone to foot injuries, ulcers and infections. Without appropriate medical care and regular foot exams, these foot infections can progress to gangrene and ultimately require amputation. Chronic kidney and liver diseases are other potential causes of peripheral neuropathy. Damage to either of these organs can result in a buildup of metabolic waste products that may irritate the nerves in the legs and feet. Disorders of the thyroid gland can also cause burning and tingling in the feet, often accompanied by muscle cramps in the legs.

Infections

Many infections can lead to inflammation of the nerves in the legs and feet. The viruses that cause chickenpox and mononucleosis are common culprits. Cytomegalovirus, human immunodeficiency virus, hepatitis B and hepatitis C viruses can trigger intense burning and tingling in the legs and feet as well. Borrelia burgdorferi, the bacterium that causes Lyme disease, can also irritate nerves in the lower extremities. A rash usually precedes joint pain and peripheral neuropathy symptoms due to Lyme disease.
Toxins and Medications

Many toxins and medications can irritate nerves and lead to burning and tingling in the feet. Alcohol is one of the most common. Chronic exposure to large amounts of alcohol is thought to lead to nerve damage. Long-term alcohol abuse is also associated with nutritional deficiencies, such as deficiencies in vitamin B12, folate and thiamine. These vitamin deficiencies can result in burning, tingling, pain or numbness in the legs and feet. Heavy metals, including lead and mercury, can cause peripheral neuropathy as well. Medications used to treat seizure disorders, certain antibiotics and antiviral drugs are also associated with peripheral neuropathy. Chemotherapy drugs used for certain cancers frequently cause burning and tingling in the feet. Common offenders include platinum-based medications, thalidomide (Thalomid) and vincristine (Vincasar). 

Autoimmune and Inflammatory Conditions

In some cases, the body's response to an infection rather than the infection itself leads to nerve damage. A condition called Guillain-Barré syndrome causes abrupt weakness and tingling in the lower extremities. Guillain-Barré syndrome occurs due to an autoimmune response wherein the body inadvertently attacks nerve tissue following a bacterial or viral infection. Left untreated, the disorder can progress to temporary paralysis and be life-threatening. Lupus, rheumatoid arthritis and Sjögren syndrome are other autoimmune disorders that can cause peripheral neuropathy. Symptoms tend to develop gradually with these conditions. Burning and tingling in the legs and feet can also sometimes occur with multiple sclerosis, an inflammatory disorder. Additional symptoms such as visual difficulties, bladder problems and muscle spasms are common with multiple sclerosis.
Tumors

Cancerous and noncancerous tumors can invade nerve tissue, resulting in peripheral neuropathy symptoms. Inflammation due to tumors that arise on or near nerves in the lower extremities can lead to burning and tingling in the feet. In some cases, cancer does not directly affect the nerves but can cause a condition known as a paraneoplastic syndrome. Paraneoplastic syndromes can result in a variety of symptoms, including muscle weakness and a burning sensation in the limbs.
When to Seek Medical Attention

In most cases, peripheral neuropathy symptoms begin gradually. If you abruptly develop burning and tingling in the feet, contact your healthcare provider without delay. If burning and tingling arise in association with muscle weakness or other nervous system symptoms -- such as visual problems, dizziness or loss of bladder or bowel control -- seek medical attention immediately. If you have an underlying medical condition, including diabetes, HIV or lupus, discuss your symptoms with your provider. Blood tests can be performed to check for nutritional deficiencies, and medications can be prescribed to ease symptoms.

http://www.livestrong.com/article/29833-causes-burning-tingling-feet/