Richard G. Petty, MD

Peripheral Neuropathy

Treating peripheral neuropathy can be one of the toughest problems facing a clinician. Peripheral neuropathy simply means disease affecting the peripheral nerves.

There are a great many cause of peripheral neuropathy. This is just a partial list to give you an idea of the things that a clinician has to think about before starting treatment:

  1. Metabolic illnesses: Diabetes mellitus; porphyria; chronic renal failure; amyloidosis and disturbances in circulating proteins
  2. Vitamin deficiencies: Vitamins, B1, B3, B6 and B12
  3. Drugs and chemicals: Alcohol; Heavy metals like arsenic, lead and mercury; organic pesticides; several drugs used in cancer chemotherapy; isoniazid; nitrofurantoin
  4. Infections: Lyme disease; Herpes zoster (shingles); Diphtheria; Brucellosis; Leprosy; Tetanus; Botulism
  5. Malignant illnesses
  6. Inflammatory and autoimmune illnesses: Rheumatoid arthritis; Systemic lupus erythematosus; Polyarteritis nodosa; Sarcoidosis; Guillain-Barre syndrome; Celiac disease
  7. Physical injury: Trauma, stretching and compression of nerves, which can include things like carpal tunnel syndrome.
  8. Congenital illnesses

Many causes of peripheral neuropathy, particularly diabetes, may also damage the autonomic nervous system that controls the heart, blood pressure, swallowing, intestinal and bladder function.

Neuropathic symptoms typically start in the feet, because the nerves running down there are longer and more vulnerable than the ones going to the hands.
The most common symptoms are:

  1. Numbness
  2. Tingling
  3. Abnormal sensations called dysesthesias
  4. A characteristic form of pain, called neuropathic pain or neuralgia: people usually describe it as “pins and needles,” a steady burning sensation or “electric shocks.” These pains can be difficult to describe: typically pains, like stubbing your toe or stepping on something sharp, are transmitted through pain fibers. Neuropathy also involves other neurological pathways, so that the brain receives impressions that it cannot process.

There has been a revolution in out understanding of neuropathic pain in recent years. It is now considered to be a disease rather than a symptom. Normal pain is designed to protect you: you put your foot on a hot plate and you pull it away immediately. Neuropathic pain is different: it is non-protective and it persists and therefore behaves like a disease.

Multiple different classes of medications have been shown to be effective in some people with neuropathic pain, though most are not approved for use by the Food and Drug Administration:

  1. Lidocaine patches and creams
  2. Capsaicin creams
  3. Opioid analgesics
  4. Tricyclic antidepressants
  5. Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  6. Anticonvulsants: Carbamazepine; gabapentin; pregabalin

Earlier this week, data presented at the European Federation of IASP (International Association for the Study of Pain) Chapters (EFIC) indicated that an innovative combination of painkillers might hold the key to unlocking the severe and relatively untreatable pain of peripheral neuropathy.

Dr Magdi Hanna, Director of Pain Clinical Research Hub at King’s College Hospital in London, has been studying the combination of the strong opioid oxycodone (OxyContin) with gabapentin (neurontin) in over 300 patients with severe diabetic neuropathy. This combination demonstrated a significant 33% improvement on top of the best pain relief achievable using the maximum tolerated dose of gabapentin as monotherapy. The study was part funded by one of the medicine manufacturers.

This study is good news, but even in this study there were a great many people who were not helped. In another blog item, I’m going to talk about some of the unorthodox approaches that have helped some people.

Restless Legs Syndrome

Restless legs syndrome (RLS) is a common (3-15% of the population) and sometimes very unpleasant problem in which people have uncontrollable urges to move their legs. If they do not move, they will begin to feel uncomfortable, painful or odd sensations in their legs, and sometimes also in other parts of the body. The restlessness may last for minutes or even hours. Movement affords people very temporary relief. The sensations are usually between the ankle and the knees, but they can also involve the thighs. If other parts of the body are involved it always makes us question the diagnosis.

The severity of the problem is highly variable, running from a mild annoyance to an incapacitating problem. In most people the symptoms are worse when sitting or at night, and often lead to loss of sleep. Not surprisingly many people feel of exhausted and irritable during the day.

With such enormous variations in the severity of the problem, and even the parts of the legs affected, it is highly likely that RLS is a symptom of a group of illnesses.

The International Restless Legs Syndrome Study Group (IRLSSG) identified four criteria that must be present for an RLS diagnosis:

  1. An urge to move, usually due to uncomfortable sensations that occur primarily in the legs.
  2. Motor restlessness, expressed as activity, that relieves the urge to move.
  3. Worsening of symptoms by relaxation.
  4. Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night.

About 80% of the people with restless legs syndrome also suffer from a separate condition called periodic limb movements in sleep (PLMS). Periodic limb movements in sleep are involuntary jerking movements in extremities, usually the legs. You can have PLMS without having RLS, and vice versa.

RLS may start at any age, including early childhood, and is a progressive disease for a certain percentage of sufferers, although it has been known for the symptoms to disappear permanently in some sufferers. The condition runs in families; children of RLS sufferers are more likely than other people to develop RLS.

It has some similarities to a syndrome known as akathisia that occurs in people taking some medications that work in the dopamine pathways of the brain. There are some subtle ways of telling the two apart, but RLS also seems to be caused by disturbances in one of the dopamine pathways of the brain.

It has been known for many years that there is an association between RLS and iron deficiency, but this link is probably not causal: just giving iron only helps a proportion of sufferers. But because of this link, everyone with RLS should have their ferritin levels tested; ferritin levels should be at least 75 mcg for those with RLS. If it’s below this level, iron supplements may help, but they are best administered by a physician, because ferritin needs to be monitored and there are down sides to taking too much iron. In a moment I’ll tell you about some very new research on iron and RLS

Caffeine and other stimulants usually make RLS worse. Restless legs syndrome frequently occurs during pregnancy. About 15% of pregnant women develop RLS symptoms during the last few months of their pregnancy. The sensations usually stop after the woman delivers the baby.

We normally divide RLS into primary and secondary. Primary RLS usually starts before age 40 and the onset is often slow. The RLS may disappear for months, or even years. But it can be progressive and get worse as the person ages.

Secondary RLS often had a sudden onset and may be daily from the very beginning. Apart from pregnancy, secondary RLS is a result of a number of medical conditions, so it is always important to rule them out. They include:

  1. Iron deficiency anemia
  2. Macrocytic anemia due to folate or vitamin B12 deficiency
  3. Diabetes mellitus
  4. Peripheral neuropathy
  5. Alcohol abuse
  6. Some types of cancer, particularly of the lung
  7. Celiac disease
  8. Renal failure
  9. Inflammatory arthritis

There have been reports of associations of RLS with other illnesses, but most seem rare. Interestingly people who undergo surgery often find that RLS symptoms become worse, which may be another clue as to the cause of the problem.

An international conference entitled SLEEP 2006, the 20th Anniversary Meeting of the Associated Professional Sleep Societies took place from June 17-22, 2006 in Salt Lake City, Utah. There were a great many interesting papers this year, including several on RLS

An international group of collaborators presented the results of the first population-based pediatric RLS survey. They used the National Institutes of Health pediatric RLS diagnostic criteria and collected data from over 10,000 families. The criteria for definite RLS were met in 1.9% of 8- to 11-year-olds and in 2% of 12- to 17-year-olds. Two different papers explored the value of using a single screening question to identify possible RLS patients. Those who answered, “Yes,” then answered more detailed questions to determine whether they met the International RLS Study Group diagnostic criteria.

A single screening question can eliminate people without RLS rapidly and direct appropriate subjects to further evaluation. Two groups of researchers found a high level of sensitivity with the question, "When you try to relax in the evening or sleep at night, do you ever have unpleasant, restless feelings that can be relieved by walking or movement?"

As I mentioned, it has been known for decades that RLS may be associated with low iron, and especially with low ferritin levels. These may be present in symptomatic RLS patients during pregnancy and in people with iron-deficiency anemia and end-stage renal disease. Previous studies had suggested that supplemental iron was beneficial for RLS patients with low ferritin levels. One paper presented further evidence of the possible efficacy of supplemental iron in the treatment of selected RLS patients with a prospective, randomized, placebo-controlled, double-blind study of RLS patients with low to normal ferritin levels (15-75 mcg/L). The RLS subjects were given either placebo or iron 325 mg twice daily and were monitored with a validated RLS symptom scale. The preliminary findings showed that the iron supplementation group had significant increases in their ferritin levels and had improved quality of life compared with those on placebo; however, the interim data presented did not show a significant change in the RLS symptom score. The study is ongoing.

Treatment for RLS is based on how disruptive the symptoms are. Apart from iron, people should review their lifestyle and see what changes could be made to reduce or eliminate their RLS symptoms. These include: Finding the right level of exercise (too much worsens it, too little may trigger it)
Eliminating caffeine
Stopping smoking
Reducing alcohol intake

Several drugs have been tried for RLS: Some of the same medications used in Parkinson’s disease, benzodiazepines, anticonvulsants like carbamazepine and gabapentin.

Last month saw the publication of an important paper indicating that the medicine pramipexole, another anti-Parkinsonan drug, helps many people with RLS

In the next article I shall review some of the other approaches used by Integrated Medicine.

A New Way of Looking at – and Treating – Inflammation

Diseases of both large and small blood vessels are two of the biggest problem facing people with diabetes. Not only is it a huge clinical challenge, but also nature sometimes does our experiments for us. The high rates of coronary and peripheral vascular disease in diabetes can be seen as a kind of experiment of nature: a recognizable set of chemical abnormalities that might shed light on vascular diseases in general. It was those twin factors: a huge clinical problem, and an experiment of nature, that lead me to pick the topic of my research doctorate. 

When I was working on my research doctorate in the mid 1980s, I came across a lot of old research that seemed to show links between inflammatory and autoimmune conditions like systemic lupus erythematosus and rheumatic fever, and the eventual development of coronary artery disease. There was also a lot of old and largely forgotten research about the link between some viral infections and the development of coronary artery disease and acute coronary artery occlusions, because some infections can make blood more “sticky.” Inflammation evolved as one of the body’s defence mechanisms.

So I made the proposal – revolutionary at the time – that diabetes, coronary artery disease and a range of other illnesses might be inflammatory rather than degenerative. I soon found inflammatory markers in people with diabetes, that helped predict when someone was running into trouble with their eyes, kidneys or heart.  Even with stacks of data, I had to spend a lot of time defending that position, because it also implied that some illnesses thought to be irreversible might not be.

With the passage of time, it has tuned out that I was probably correct. Chronic inflammation, wherever it starts, mat have long-term effects on the body and on the mind. Chronic inflammation increases the risk of diseases of many blood vessels, as well as causing anemia, organic depression and cognitive impairment. Here is a partial list of common conditions in which inflammation is a prominent factor:
1.  Rheumatoid arthritis
2.  Systemic lupus erythematosus
3.  Fibromyalgia
4.  Chronic infections
5.  Insulin resistance or metabolic syndrome
6.  Arteriosclerosis
7.  Diabetes mellitus
8.  Hypertension
9.  Asthma
10. Inflammatory bowel disease
11. Psoriasis
12. Migraine
13. Peripheral neuropathy
14. Alzheimer’s disease
15. Autism
16. Gingivitis
17. Cystitis

The reason for raising the issue is not to say “told you so!”

It is instead that we need to think about inflammation a little differently. There is a mountain of information about the physical aspects of inflammation. We can stop at the simple description of inflammation as a condition in which part of the body becomes reddened, swollen, hot, and usually painful, or we can look below the surface: we can examine inflammation not only as a physical problem, but also as a psychological, social, subtle and spiritual problem. Why bother? Because the deeper approach allows us to understand and to treat and transcend inflammation as never before.

I am going to write some more about specific ways to address inflammation and what it means in future articles. I would also like to direct you to the book Healing, Meaning and Purpose, in which I talk about specific approaches in more detail.

But I would like to start with this.

In Ayurvedic and homeopathic medicine, inflammation is a sign of an imbalance in the vital forces of the body, and the traditional Chinese system agrees: here inflammation is usually a manifestation of an excess of Yang Qi, or a deficiency of Yin Qi. Most of our lives are seriously out of balance: Yang Qi is like a rampaging lion that has been stimulated by:
Acidic foods;
Environmental toxins;
Unwanted sexual stimulation:
Discordant music:
Constant demands from others:
Toxic relationships;
Years spent in front of television sets and limitless multi-tasking.

It should be no surprise to learn that all of these inflammatory conditions are increasing rapidly throughout the Western world. Not because we are getting better at identifying them, or we are living longer, but genuinely increasing.

It is wrong to put all the blame on poor diets or inadequate exercise. The problem is more subtle and is a reflection of distorted Information being fed to our bodies, minds, relationships, subtle systems and spiritual relationships.

The great news is that this simple conceptual shift gives us a whole load of new tools for handling these problems, and for using them as catalysts to growth.

In the next few weeks, I am going to drill down and give you some specific guidance that ties into the material in Healing, Meaning and Purpose and the next two that are on the launch pad.

Fasten your seat belt!

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