Wednesday, 29 July 2015

Eighty Six Year Old Inventor Invents Solution For Neuropathic Pain

Today's post from (see link below) is a long one but what a great one to read! Not only is this guy's invention a serious breakthrough in the treatment of neuropathic pain but the story behind it is truly inspiring. If you don't read anything else this week, read this one - it'll brighten up your day!

The genius inventor who says he’ll eliminate chronic pain with a simple device

By Terrence McCoy July 27 at 6:00 AM 


Robert Fischell is Maryland’s greatest inventor. (Photo by Toni L. Sandys/ The Washington Post)

At exactly 1:45 p.m. on a Tuesday, one of the nation’s most prolific inventors arrives at an International House of Pancakes via sports car. It gleams quicksilver in the afternoon sun. “They call this a Jaguar,” purrs Robert Fischell, who’s credited with saving tens of thousands of lives and ushering in the modern era of satellite navigation. “I think it’s named after a cat.”

Then Fischell, in a collared shirt unbuttoned low, puts the Jag into action, weaving it through traffic on his way toward the University of Maryland. He has a meeting there at 2 p.m., and it looks to be an important one. The tech guys are rolling out his newest invention. And this one — a contraption he says could cure chronic pain — should be a doozy.

The life of Robert Fischell has been one of doozies. A space scientist turned inventor, Fischell has authored more than 200 patents that range from the grave to the quirky. He has invented a rechargeable pacemaker, an implantable cardiac defibrillator, a device that warns of epileptic seizures, an insertable insulin pump and a gizmo that zaps migraines before they start. He has also fashioned a bevy of penile prosthetics to cure erectile dysfunction as well as something called a “bowl for keeping cereal crispy.”

But this invention, he says, is his most ambitious yet. “Chronic pain costs the American people $600 billion every year,” Fischell says in a lilting staccato flecked with traces of his Bronx youth. “Six. Hundred. Billion. Dollars.”

Still, Fischell is not a young man. He’s 86. He’s had two surgeries for cataracts in the last six weeks. He has an artificial left knee.

Fischell, who grimaces when mortality arises in conversation, knows more days are behind him than ahead. So he keeps a frenetic pace. He clocks 10-hour days at his office. He drives his Jaguar fast. He drinks unsweetened tea by the quart. This could be his last great invention. He has to finish it soon.

It’s now 1:55 p.m. Fischell slams the Jaguar into a parking space. He hustles into the Fischell Institute for Biomedical Devices, arriving at a conference room. Fischell looks around. It’s empty. He’s early.

The language of pain

The first scientist to join him is Lex Schultheis — a man who’s ready to talk pain. Schultheis wears camouflage moccasins and an arm sling and has ruffled white hair. Some weeks back, Schultheis said, he took a bad spill while astride his unicycle and “fractured my arm into a hundred pieces.” It hurt like something else. But that, he said, was a good thing.

“There are two kinds of pain,” said Schultheis, the director of the university’s innovation initiative. “Good pain and bad pain. There’s the pain that prevents you from reinjuring yourself,” which he experienced after his unicycle accident. But then there’s “bad pain,” he said. “It’s when the repair is done and the doctors have done everything they can. It’s not serving a purpose.”

One-third of Americans know what Schultheis is talking about. We live in an era of chronic pain. It batters more people than diabetes, heart disease and cancer — combined. The answer thus far has been painkillers, and the number of opioid prescriptions have tripled in the last 15 years, according to the CDC. This, however, has been a deal with the devil. Between 1999 and 2010, the number of opioid overdoses surged from 4,000 to 16,500 amid mounting evidence suggesting that painkillers actually increase pain sensitivity.

That got Fischell thinking. What if drugs aren’t the answer? What if they communicate with nerves in the wrong language? What if it’s time for a new language?

If the body is a house, the nervous system is its electrical wiring. The network, which has millions of entry points throughout the body, communicates in electrical pulses. A finger prick shoots a series through a long axon to the spine — the pathway that all pain signals must pass — until they strike the brain. The higher the frequency of the nerve’s signal to the brain, the greater the pain.

So Fischell, now holding forth at his meeting, said the best way to calm down those nerves is to speak to them in a language they understand — electricity. The problem, of course, is that electricity kills. Wouldn’t it do more damage than good? Fischell laughed at the question like he was in on a secret joke. The answer, he said, was just around the corner.

A barrel-chested engineer named Wes Lawson materialized at the doorway. Fifteen minutes late, he wheeled in a large metallic box of blinking lights and dials. A long cord affixed to a copper coil dangled from its side.

This was Fischell’s latest invention. This device, he said, interrupts a pain neuron’s electrical signal before it reaches the brain. And the best part, Fischell said, is that it doesn’t use electricity at all. It uses magnetism.

‘A major step forward’

If there’s a moment that marked the genesis of this device, it came 15 years ago in the mountains of New York. There, ensconced inside at the Mohonk Mountain House, sat Robert Fischell with his son, a physicist, and a neurologist named Adrian Upton. They called their meeting an “innovation retreat.”

“I don’t know why it is, but the three of us could always get together and invent stuff,” said David Fischell, who holds 85 patents and helms several biomedical companies that have commercialized the family’s inventions. “So we went to this quiet spot and we literally spent five or six hours a day for two days talking about different areas where electric stimulation could help.”

No one can remember the details of who said what. But at some point, one of the three inventors brought up migraines. The brain, they reasoned, was a natural place to use electricity. “If pacemakers and electricity works for the heart, then it should work for the brain considering it’s much more electrical than the heart,” David Fischell said. But the trick was to get the electricity to the brain. So they mulled a concept in physics known as Faraday’s law of induction. The principle, which also gave rise to electromagnetic generators, holds that a pulse of magnetic energy will induce an electrical current. And that, they thought, might grant them a way into the brain.

Diagnostic researchers had already used this technology — called transcranial magnetic stimulation — to poke and prod the brain with bursts of electricity. But no one, David Fischell said, had used it to treat the brain.

So Upton, back at his office in Ontario at McMaster University, fired a pulse of magnetic energy into the skull of a patient who complained of migraine pain and an aura. The patient’s aura then shifted shape and size. This suggested something big: Electricity could affect the neurons behind the migraine. “The overall principle is very straight forward,” Upton said. “Migraines are like epilepsy in that there is an electrical spreading in the brain, and if you can interrupt that spreading, you could stop the migraine.”

In 2000, the three inventors filed an application for a patent. It detailed a portable device that presses against the skull and shoots magnetic energy into the brain, expunging a migraine before it starts. One study published in Neurology called such technology a “major step forward” in chronic migraine treatment. Another study in Neurological Research found that 50 out of 51 migraine patients reported a 50 percent reduction in headache frequency after one week of treatment. The Journal of Neurological Sciences said it “ameliorates chronic migraine” in one part of the brain.

Still, 13 years passed before the Food and Drug Administration approved Fischell’s device. In those 13 years, a lot of life happened. Fischell started a department of biomedical engineering at the University of Maryland. He criticized the FDA at a Congressional hearing for what he called its sluggish pace in approving patents for consumer use. And his wife of 54 years died of leukemia.

It crushed Fischell. For a man who has hung a sign that says “nothing is impossible” in his office, he couldn’t accept his own helplessness. “I couldn’t save her,” said Fischell, who watched his wife’s deterioration in daily doctor visits. “I’m an inventor. I invent things. But I couldn’t come up with anything that could save her.”

A little more than a year after her death, Fischell married his former secretary, which surprised his three children. “It seemed a little fast,” son Tim Fischell said. “But he is not someone who does well alone. He is not someone who would be OK alone, but he and his [new wife, Susan] had known each other and now are very devoted.”

And it was this relationship that inspired Fischell’s greatest pursuit yet: his quest, at 84, to eliminate chronic pain.

The migraine headache device invented by Robert Fischell. (Photo by Toni L. Sandys/ The Washington Post)

‘Inventing is a blessing and a curse’

Fischell lives inside a cavernous ranch-style home tucked among trees on an estate he calls “Willow Oaks.” He rarely leaves it. He holds meetings there when he can. He takes meals at the nearby Crossroads Pub. He hangs out with neighbors. One such gathering came in December of 2013 when one neighbor, a woman in her seventies, was dying of cancer.

“She’s telling my wife how severe the pain is in her feet from two years of chemotherapy,” Fischell said. “There are 10 million Americans with severe foot pain. And my Suzie, who doesn’t even have a college degree said, ‘Well, why don’t we use Bob’s migraine device to erase your foot pain?’ And I said, ‘What the hell are you talking about?’ A migraine is a migraine. This is foot pain.” But the suggestion nonetheless stayed with him. Possibilities sloshed around in his mind that whole night. He wondered: Could the same principles that govern the migraine invention do the same for chronic pain?

Fresh research suggesting receptors in the meninges produce migraines has emboldened Fischell’s hypothesis. If electrical currents can disrupt pain receptors in the meninges, it might do the same for other parts of the body. So Fischell has spent weeks drawing. He has drawn a boot-shaped contraption that someone can slide their foot into to receive a jolt of electromagnetic energy. He has drawn a shoulder harness that targets the rotator cuff. He has drawn a belt festooned with a giant copper coil that someone with back pain can wear. He gave his technicians weeks to forge 10 prototypes that he can use in a clinical trial beginning in September to test his hypothesis.

Everything’s moving fast — but is it too fast? Fischell’s career, after all, was forged in space laboratories at a time when astronauts were shooting off to the moon and everything seemed possible. That optimism has informed his decisions in innovation. And while it has driven him farther than most, it has also misguided him at times. (It’s unclear, for instance, who will need a cereal bowl that ensures crispy corn flakes.)

“Folks who don’t know him that well may be suspicious of his optimism,” Schultheis said. “He’ll tell you that this will cure all pain. And while he’s not unrealistic, there are projects that he works on that aren’t successful.”

Fellow inventor Upton agrees: “This isn’t something that’s going to happen over night as some sort of miracle. That’s not realistic. But there’s no question that the type of stimulators he’s working on now help pain, no question.”

But Fischell’s not interested in talking about things that can’t happen. He’s not interested in discussing his age, or his mortality. He’s not interested in considering what he’ll do when the work stops.

As he departs his meeting on a recent Tuesday and climbs into his Jaguar, he says he’s interested in getting back home to his office. There’s so much work to do. There’s no time to waste.

“Inventing is a blessing and a curse,” he said. “But it’s fun, too. It’s a game. But the stakes of this game couldn’t be graver.”

Tuesday, 28 July 2015

VM202 - More Gene Therapy Evidence For Neuropathy

We've mentioned the subject of today's post from (see link below) several times already but this article explains this exciting new development in terms that almost everybody can understand. Certainly worth talking over with your doctor or specialist and maybe even getting your name onto some trial lists in your area (you may have to fight for that one). However, the idea of 8 injections per year taking away most of our pain, is a very attractive one - let's hope this is a development with real substance. Well worth a read.

Can Gene Therapy Reverse Diabetic Neuropathy?
John Schieszer, MA July 24, 2015 

  A nonviral gene therapy may relieve symptoms of painful diabetic neuropathy.

Gene therapy in the form of a plasmid containing two human hepatocyte growth factor isoforms administered via intramuscular injection may alleviate symptoms and improve quality of life in patients with painful diabetic neuropathy.

In addition, the plasmid —VM202 — may be particularly beneficial in those patients not taking gabapentin or pregabalin, according to researchers at Northwestern University.

In a recently completed double-blind, placebo-controlled study, 84 patients were randomly assigned to receive injections of 8 mg or 16 mg of VM202 per leg (calf muscles and lower leg) or placebo, with doses administered on days 0 and 14.

At 3 months, patients in the low-dose group experienced a significant reduction in pain compared with the placebo group, the researchers found.1

“I am very excited about it. This is an enormous problem, and it has a huge impact on people's lives. [These patients] spend so much time in agony,” said study investigator Jack Kessler, MD, who is a professor in the department of neurology at Northwestern University Feinberg School of Medicine in Chicago.

“The data are very, very strong. One issue that remains to be resolved is if we are modifying the disease, and at this time, the jury is still out. In our last study, we had some improvement in patients to feel light stimuli, but we need additional data to say we are altering the course of the disease. If our phase 3 study gives us the same results, then this treatment will be the best option for treating diabetic neuropathy.”

Study Results

The primary outcome for this current study was change in the mean pain score measured by a 7-day pain diary. The analysis also included quality of life and pain measures, and measurement of intraepidermal nerve fiber density, according to Kessler.

The study showed that patients receiving 8 mg of VM202 per leg improved the most in all efficacy measures, including a significant reduction at 3 months in the mean pain score. The reductions in pain continued but were not statistically significant at 6 and 9 months.

“We would probably inject patients four times a year. If it turns out that we are actually making the neuropathy better, then it is reason to think patients would graduate from this, but if it turns out we are just treating the symptoms and not the disease, then we would see injecting the patients four times a year,” Kessler said in an interview with Endocrinology Advisor.

The mean age of the patients in this study was 60 years (approximately 75% men), and the mean duration of diabetes was 15 to 16 years.

The researchers found that 48% of the patients experienced at least a 50% reduction in pain in the treated group compared with 17% in the placebo group. The study also demonstrated significant improvements in the brief pain inventory and the questionnaire portion of the Michigan Neuropathy Screening Instrument.

The researchers noted that the largest reductions in pain were found among patients not on pregabalin or gabapentin.

There were no significant adverse events attributable to VM202 and this treatment was deemed safe and well tolerated. 

More to Learn

It is hoped that VM202, which contains a human hepatocyte growth factor gene, will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and subsequently reduce the pain.

“We believe we are getting a two-for-one treatment. We are supplying nourishment to the nerves, but we are also helping to improve blood vessel function,” said Kessler. “The most remarkable thing is that we pushed the dose up and we had literally not one serious side effect in the entire trial, only [injection] site soreness.”

A large trial is now planned, and the researchers hope to enroll 475 patients at 20 sites across the United States starting in December.

Amanda Peltier, MD, who is an assistant professor of neurology at Vanderbilt University in Nashville, Tennessee, said these study findings are interesting, and this approach could represent a new way of treating diabetic neuropathy with fewer treatment-related adverse effects.

“There is a huge unmet need for diabetic neuropathy as the current medicines have side effects and do nothing to improve or retard the progression of the underlying neuropathy, only treat the pain. In addition, our understanding of diabetic neuropathy has improved for type 1 diabetes, but there has been little headway in improving neuropathy for patients with type 2 diabetes,” Peltier told Endocrinology Advisor.
Looking Ahead

According to M. Sue Kirkman, MD, who is a clinical professor of medicine and the medical director of the Diabetes Care Center Clinical Trials Unit at the University of North Carolina School of Medicine in Chapel Hill, this is a quality of life issue.

Although there are several medications that may help symptoms, they are not effective in all patients and may come with significant side effects, Kirkman said.

“This trial showed promising results, but was relatively small and short-term. Larger and longer-term trials will be important to see if the benefits pan out, and also to get a better feel for potential adverse events. Up to now, treatments for diabetic neuropathy have been purely palliative, with no interventions that seem capable of actually improving nerve function,” Kirkman told Endocrinology Advisor.

“There are some hints from this study that this agent could actually improve nerve function. If that pans out in larger trials, it would be very exciting, since lack of feeling in the feet from advanced diabetic neuropathy is a risk factor for foot ulcers and amputations.”
Kessler JA et al. Ann Clin Transl Neurol. 2015;2(5):465-478.

Monday, 27 July 2015

Acupuncture Prevents Neuropathy During Cancer Treatment

Today's interesting post from (see link below) looks specifically at how acupuncture can prevent neuropathy developing during cancer treatment. It's a startling claim and one that could be extrapolated to apply to other forms of neuropathy if you follow the logic behind it. However, acupuncture is still getting a bad press in some quarters and there's no doubt a little blind faith doesn't do any harm. However, if the science is sound then it could be an important breakthrough. The acupuncture terminology in the article may leave you a bit baffled, so you may need to go to a basic acupuncture site to discover what it all means but there's no harm in talking to your doctor or specialist about it and maybe a qualified medical acupuncturist too (to get a balanced view).
Acupuncture Alleviates Chemotherapy Peripheral Neuropathy No author given on 24 July 2015.

Researchers find acupuncture effective for alleviating chemotherapy induced peripheral neuropathy (CIPN) for patients with colon cancer. Neurotoxicity from chemotherapy may damage nerve fibers and lead to symptoms including pain, burning sensations, tingling, muscle weakness, balance disorders, paresthesia, dysesthesia, cold or heat sensitivity in the hands and feet, and a “glove and stocking” distribution of symptoms. The paresthesia is often experienced as a bilateral pins and needles sensation. Severity ranges from mild to debilitating. The researchers summarize their findings into three main benefits of acupuncture for patients with CIPN: 

Acupuncture administered prior to chemotherapy prevents CIPN.
Use of acupuncture during chemotherapy inhibits the progression of CIPN.
Administration of acupuncture after completion of chemotherapy eliminates or reduces persistent symptoms.

The research was conducted at the Cancer Treatment Centers of America at the Southwestern Regional Medical Center located in Tulsa, Oklahoma. The investigators applied Traditional Chinese Medicine (TCM) style acupuncture to 10 patients with chemotherapy induced peripheral neuropathy. They note that “all of the patients reported or had improvement in their CIPN grades after starting acupuncture.”

The researchers note that using customized acupuncture point prescriptions in the TCM style produces superior patient outcomes when the use of distal acupuncture points are employed. The researchers emphasize the need for customization of the acupoint prescriptions per each patient’s differential diagnostics for maximum clinical efficacy. In addition, they emphasize that distal acupoints “increase blood flow” and therefore have an especially important role in the treatment of CIPN.

The researchers note that CIPN symptoms are “typically dose-dependent”. As a result, CIPN may limit the amount of chemotherapy a patient can tolerate thereby interfering with the efficacy of anticancer therapy. This is particularly prevalent with drugs containing platinum including oxaliplatin, an important drug in the treatment of colorectal cancer.

Platinum based medications often have both acute and chronic adverse CIPN effects because they “produce direct damage to dorsal root ganglion (DRG) neurons.” The researchers add, “Cisplatin, taxanes, and vinca alkaloids have also been shown to exert damage to microtubules resulting in the disruption of axonal transport and thereby signal transduction in these nerve fibers.” The researchers note that “acupuncture for the treatment of CIPN has several advantages.” They note that “side-effects are minimal and it has been shown to be safe and effective in preliminary studies.” An additional benefit to antitumor therapy, they add that studies indicate that acupuncture regulates the immune system. 

Full body acupoints on a doll.
Acupuncture Treatment
The researchers note that the data indicates that “TCM-based acupuncture, prescribed frequently and aggressively, and focused on the distal extremities may be effective for preventing and treating CIPN.” They add that an aggressive treatment would, at a minimum, employ the following acupoints:

5 NP (Five Point Ear Acupuncture Protocol)
Ba Feng
Ba Xie

Supplementary acupoints include:

Sheng Ba Feng
Sheng Ba Xie
Jing-well acupoints
Yin Tang

The researchers note that aggressive acupoint therapy was not always needed to produce clinical results and some patients are too weak to receive aggressive therapy. All acupuncture needles used were between 1/2” to 1” in length and were between 36 - 38 gauge. For this investigation, DongBang brand acupuncture needles were used. For the Ba Feng, Ba Xie, and Jing-well acupoints only guide tube insertion of the needles was employed. Needle retention ranged between 10 - 45 minutes per acupuncture treatment session with an average of 20 minutes per session. Electroacupuncture was not administered.

The research indicates that an integrative medicine approach to chemotherapy for colon cancer patients has several benefits. Patients experience an improvement in the quality of life including better functionality and comfort. In addition, reduction or elimination of CIPN reduces symptomatic interference with the quantity and frequency of chemotherapy treatments. The researchers note, “In the current authors’ treatments, the goal is to combine Eastern and Western practices in order to best provide for the patient.”

Acupuncture Theory

The investigators provide TCM theory as it relates to CIPN. According to TCM principles, CIPN is caused by qi and blood flow abnormalities. They note that blood nourishes tissues and qi moves blood to the tissues. The researchers note, “CIPN results from the body lacking nourishment to the muscles (Blood) and the body not directing the Blood to the limbs (Qi).”

The authors provide TCM theory as it relates to colon cancer. Tumors are often a form of stagnation resulting from disruption of circulation. Heat stagnation is also common with colon cancer patients and is indicated by “an area that feels hot to the patient, red tongue, rapid pulse, dry stool, and constipation.” Toxin stagnation is also common and is often produced by exposure to chemotherapy. Phlegm or damp stagnation is common with fatty tumors and is often concomitant with the following symptoms: mucus in the stool, loose stool, slippery pulse, puffy tongue, a feeling of heaviness. Qi stagnation may occur and is characterized by: flatulence, bloating, irritability, moving pain, purple tongue. Blood stasis is indicated by sharp or stabbing pain, an immovable tumor, dark stools, and difficulty with defecation.

The authors note that their overall clinical impression of cancer patients is that they have a deficient constitution. They note, “the body is not strong enough to move energy to all of the tissues. Therefore, the energy stagnates. This is often the case with CIPN.” They add, “Acupuncture is an effective treatment option for CIPN because acupuncture not only stimulates the body to send blood flow to the site of the needle but also helps strengthen the underlying condition of Deficiency.” The authors note that by applying acupuncture to the extremities “it will act as a local therapy bringing Blood and nourishment to help treat the damage caused by chemotherapy.” Moreover, the authors note that “by strengthening the body against its underlying Deficiency, acupuncture helps restore balance to the body.”


Valentine-Davis, Brandy, and Laurence H. Altshuler. "Acupuncture for Oxaliplatin Chemotherapy–Induced Peripheral Neuropathy in Colon Cancer: A Retrospective Case Series." Medical Acupuncture 27, no. 3 (2015): 216-223.

Tagliaferri M, Cohen I, Tripathy D. Complementary and alternative medicine in early-stage breast cancer. Semin Oncol. 2001;28(1):121–134.

Sunday, 26 July 2015

The Story Of An Author's Struggle With Multiple Health Problems

Today's post from (see link below) is the personal story of an author, whose health problems put most of our own problems firmly into the shade. There are few enough well-known people who confess to having neuropathy but when they do emerge, they remind us that neuropathy and other diseases are no respecters of status or fame. Jane Green's story may just help you put your own situation in perspective and make you thankful for small mercies.

Queen of 'chick lit' Jane Green on coping with life's ills
By Nottingham Post | Posted: July 25, 2015
Author Jane Green

Once upon a time – last May to be exact – Eva Cassidy saved Jane Green's life. If she hadn't received a CD present of the late Fields of Gold singer, the author might never have discovered the malignant melanoma on her leg, which was spreading.

"It was May 31 – a friend of mine had given me the CD for my birthday," recalls US-based Green, 47.

"When I played it, I thought how have I never heard of this incredible singer, so I Googled her and found she had died of melanoma. That night, I was lying in bed, and my eyes fell upon a tiny little mole, and there was something that didn't look right.

"It had a black splodge in the middle of it. I looked at it and I knew."

Green, meeting me over coffee to discuss her new book, Summer Secrets, went to see a dermatologist immediately, who confirmed her fears.

"We have quite a jovial, jokey relationship. When she looked at my melanoma, her face went very serious. And then she phoned 12 days later – I was on a train coming back from New York, and she said, 'so you have time to talk? It's cancer'."

Within days of the diagnosis, Green had turned herself into "one of the world's leading experts", says the mum of four, with a laugh. "Part of how I deal with things is by informing myself. I need to know everything about everything."

But what came with that knowledge were frightening statistics: "I knew that if it was in my lymph nodes, the numbers were not quite as good."

She's a self-confessed lifelong sun worshipper and says melanomas diagnosed today are from sunburn in adolescence. But there's also a genetic element, as her uncle died from malignant melanoma. Luckily for Green, the cancer was caught before it had spread and she is now cancer-free.

It was the latest in a string of health problems the author has faced over the last four years, starting with a deer tick bite in 2011 that gave her Lyme disease.

"I'm a gardener, so I remember pulling ticks off, but I never had a rash and never thought I'd get sick."

The disease sparked a massive autoimmune response, giving Green terrible migraines and exhaustion: "There were days when I couldn't walk up the stairs. I'd take one step and collapse on the steps crying."

She also has Hashimoto's disease, where your immune system attacks your thyroid gland and you gain weight; suffers neuropathy ("the nerve endings went in my hands and my feet") and Raynauld's syndrome, affecting her circulation.

"I'm extraordinarily strong and I don't really know any other way to be. I just plough through," she says of coping with life's storms.

Green managed her symptoms by cutting out dairy and carbs for a year, and has never felt better.

Hardest of all was giving up sugar and during that year, she started going to Alcoholics Anonymous – although she wasn't really an alcoholic.

"I'm not a very good drinker, I'm a lightweight. But I had given up alcohol because I was trying to recover from exhaustion. I'd been around 12-step programmes for a long time, and the only requirement for membership is the desire to stop drinking, so I started going to meetings.

"I have that addictive, compulsive personality; alcohol just happens not to be my drug of choice, but I really do understand it, because I have that gene.

"There's this fear and it allows us to think we couldn't possibly be alcoholic because we're not rolling around, drunk in the street. But actually, it's just drinking more than other people."

At the meetings, she found "tremendous wisdom", some close friends - and the inspiration for her latest novel.

Summer Secrets centres on Cat, who we meet as a hard-drinking twenty-something journalist in London. She learns from her American mum that her father wasn't her real father and in fact, he's still alive and an artist living in Nantucket. So Cat flies to meet him and her two half-sisters, but ends up alienating her new-found family when her drinking gets out of control.

Green says the story of a discovered family is actually that of her husband's cousin, who in his 50s learned he had a father and brothers he knew nothing about.

"He had this tremendous sense of coming home and has continued to have an extraordinary relationship with his brothers."

Although Green was also a journalist, she never drank herself into a stupor as Cat does.

She published her first novel, Straight Talking, at 27, married an American and moved across the Pond at 32. She had four children, went through a divorce, married again in 2009 after a chance encounter with the landlord of a holiday cottage and is now settled on the Connecticut coast with her "blended family" of six kids.

"Frankly, most of the time I'm just treading water, trying to keep my head above," she says of motherhood. "You muddle through. I'm very strict on manners. But with technology, I feel like I'm fighting a losing battle. Life is so busy and even with the best intentions in the world, I just do the best I can."

Summer Secrets by Jane Green is published by Macmillan, priced £12.99. Available now.She has a little office at the Westport Country Playhouse, where she goes to write each morning, while the children are at school, and is grateful for having her own space and identity.

"I live in a town that's an hour outside of New York where most of the men work, and their wives don't, because it's a status symbol to not work. And these are smart women; they have wonderful degrees from the best universities in the country.

"I've always felt so lucky that I have the perfect job. I get to work and I'm defined by something other than being someone's mum or someone's wife. I have something that's entirely mine, and I also get to be a full-time mother."

While life in America is "easy", she misses the British sense of humour and that Brits "don't take themselves too seriously".

Refreshingly, in a culture obsessed with body image, she makes a stand by not hitting the gym ("On principle, I refuse"), and she's branching out with a cookbook - Good Taste - and has a furniture line in the offing.

Her 18th fiction book is starting to take shape in her head too, even if she's not sure whether the 'chick lit' tag still fits.

"I'm proud of having been at the forefront of this huge genre in fiction, but that was almost 20 years ago, so I don't think I'm writing chick lit any more; it feels young. I'm 47 and I defy anyone to call me a chick these days!"

And with that, she drains her Americano and heads off to meet her school friend and chick-lit contemporary, Freya North.

Saturday, 25 July 2015

Three Ways Of Dealing With Chronic Neuropathy Pain

Today's post from (see link below) is a self-help article designed to help you reduce your suffering by non-medical means - i.e. psychology. Now I know that many of you hate this sort of post with a vengeance but the trouble with extended clichés, is that they irritatingly contain so much truth and that's the case here. So this sort of mind-yoga can really help if you accept that many of the platitudes really do apply in your case, - however much you may not want them to. Forget the preconceptions; read it and see if there are one or two tips that could genuinely help you live better with your neuropathic pain - you may surprise yourself. For non-cynical, self-help and motivational-thinking fans - this article is one of the better approaches to dealing with pain.

3 Ways to Weather the Internal Storm of Chronic Pain and Not Let it Define You
February 13, 2015 by Princess 

Pain is so all-encompassing, so constant, and overwhelming, it can be difficult to detach the pain from everything else in life, especially when it so deeply affects everything in life. From the outset, it may appear as if we entirely define ourselves by our pain. After all, it needs to be considered before, during, and after every task or activity, even the most passive activity. But this is part of managing our chronic pain, trying to live, and cope as best we can in spite of the pain.

When the pain takes over more than your body but your mind and spirit too, it’s natural to become depressed or struggle with our feelings and perception of ourselves. When so many dreams are reluctantly let go of because, now, after perhaps many years of pain, they cannot come true, it can be even easier to define ourselves as the ‘one with pain’.

Yet in doing so, letting go of the you that’s you, even subconsciously, as you navigate the lunacy that is living with a severe pain condition leads to a different kind of internal imbalance. Sadness, depression and even heavier thoughts about all the pain has affected, or taken away can churn relentlessly in your mind but only serve to make you feel worse. If your thoughts are churning like the darkest of skies, try the 3 techniques to help you calm the internal storm below.

Your Pain Does Not Define You

Pain may have made you sad, angry, feeling hopeless, and lost, or made your temper short at times, but pain is designed to get your attention, to make you take notice. Obviously with acute pain this is useful but with chronic pain the signals are on a vicious loop. There’s no reason for your body to be firing these excruciating signals but as it believes there is a problem, and danger, it reacts just the same.

Be kind to yourself not hard on yourself for even the strongest are weakened by pain, whether that’s hidden or not. Constant pain is like a toddler forever tugging at your skirt, and even the most compassionate of mothers would lose their calm equipoise after a decade or more of skirt-tugging. OK the metaphor doesn’t quite articulate the lunacy or limitations, the loss or the lack of living, or the seemingly insurmountable strength needed to keep going, keep surviving, in spite of pain, but attention-wise, it’s a constant pull. That alone would test the strongest of souls.

“It is true that pain often changes people,” says Dr. Linda Ruehlman, social/health psychologist and director of the Chronic Pain Management Program. “You may have lost some of the positive abilities that defined you. These losses are powerful and sad, and coming to grips with them is a process that will likely take some time. Don’t let the pain overwhelm your image of who you are. Sometimes thoughts can be so negative that you may have trouble realising that pain doesn’t define you.”

Remember What You Like About Yourself

Chronic pain and illness impacts everything so it’s entirely human to feel that you are ‘not yourself’. You may feel that others are also treating you like ‘the one with pain’, as opposed to the ‘old you’. In changing how you are treated by loved-ones can have such a huge effect. It acts like a subconscious confirmation that things will never be the same and you must now be this ‘ill person’.

You may even feel a sense of shame in having your condition, when our body doesn’t serve us as society leads us to believe, that is, it doesn’t ‘get better’, we can feel a sense a failure, no matter how unjust. “While you are adjusting to any temporary or possibly enduring losses or changes that are part of your chronic pain, don’t forget that you still have positive qualities,” says Dr. Linda Ruehlman.

“Remembering the positive may help you to cope and may decrease depressing thoughts. It can be easy to focus on the negative at the expense of the positive. Take some time to review what you still like about yourself.” You may have a great sense of humour but have become disconnected from that lighter side of life because of pain taking over. You may have stopped doing things you love, but in losing that part of you, you’ve lost a little more of yourself.

You Are Not Your Pain

Your pain may try to define you, it may, and likely has taken over your every waking moment, every sleeping moment too. We may not be what happens to us but must survive it. We are not the grief we feel, nor anger, loneliness or even loss. We are not the dark, rumbling storm that is our constant pain and sadness but we must weather it.

That weather may be, and probably is, the worst weather in the world but even on the most difficult days, even on your darkest days, the toughest, most challenging nights too, how you speak to yourself, the compassion you have for yourself, and ability to allow your feelings room to be expressed through all the challenges is crucial to wellbeing, resilience and your ability to cope.

Those storms might have run wild and torn through the skies of our lives, ripped out forests of hope and destroyed all in its wake but even then, we are not the storm. To paraphrase Pema Chödrön, we are the sky, everything else is the weather. No matter how you are feeling right now, you are not your illness. By virtue of being here and living through this at all, you are a miracle, made all the more miraculous for being so strong.

No matter the intensity of this particular storm, you’ll weather it. You’re weathering it right now. The storm may never completely abate but the worst days do improve, flare-ups do lessen, even the darkest days do eventually allow in a little light. Even the deepest despair will lift, even if only momentarily. You might be affected, made stronger, or even weaker but that’s not the point. The point is you’re already surviving, already weathering the storm like a champ. But if its a little too wild right now, read on.

If your thoughts are churning like the darkest of skies, here are three techniques to do calm the storm and cope with your internal weather.
Here are 3 ways to calm the internal storm of living in pain:

Calming the Storm with Visualisation

You are not your feelings or your moods, you are not your depression, your anxiety, your frustrations. You are not your pain. Make a regular practice of mentally stepping back form difficult feelings or dark thoughts when they occur. One technique used in Acceptance and Commitment Therapy is to distance yourself from the thoughts, to not engage with them by using this visualisation.

When the incessant chatter seems unending is to imagine your thoughts as leaves on a stream. Allow yourself to pause, breathing gently, evenly and smoothly, and visualise your thoughts as leaves floating down the stream. As the leaves are slipping by, watch without touching them or picking them up and thus engaging with them. Simply allow the leaves to float down the stream without affecting you and keep breathing, calm and present.

An alternative to this effective technique to visualise these feelings as passing clouds in an otherwise blue sky. See them pass, name them should it help you, then watch them pass without connecting to them. Let them go. Instead of stopping each thought, you allow it to pass by untethered, with you, in serene stillness watching the sky. Using Pema Chödrön’s quote is an empowering way to see this challenging situation, the lost life, and your response and feelings about it all.

“You are the sky. Everything else – it’s just the weather.” ~ Pema Chödrön

Calming the Storm with Psychology

The following techniques are designed to help you learn to recognise the thoughts that only serve to increase your suffering and keep you trapped in the darker places. I’ll expand on this more deeply but the first step in healing unhelpful thinking is simply to be aware of what you are thinking. Simplistic as it sounds, when you pause to notice what your mind is saying it creates a space between you and your thoughts, in turn affording you the opportunity of choice.

Worst case scenario worries make it even harder to cope with chronic pain, more difficult to sleep at night, and also create such a increased level of tension that it is difficult to calm your pain, relax or feel any kind of joy. You may be having difficulties coping, not to mention years of ‘evidence’ that the pain is getting worse or your future is bleak but focusing on that, going over and over that in your head, not only makes you feel worse but increases your physical pain too.

The following technique is borrowed from ACT (Acceptance and Commitment Therapy), which was developed from CBT (Cognitive Behavioural Therapy), and there is power in its simplicity. When your inner voice is telling you that it’s hopeless, that you’re getting worse, not coping, never going to improve or manage, or have [insert goal/hope/dream here], name the thought and say to yourself, “Ooh here’s the ‘I’m never going to improve/manage/cope/only getting worse’ ‘story’ again”.

Worst case scenario worries make it even harder to cope with #chronicpain.

The thought may still exist but after you redirect your focus to the present moment, you do not become caught up by it, follow it, end up on one of those horrid trains of hopelessness and depressing thoughts that only serve to make you feel a thousand times worse. See it as a story you tell yourself. If you feel stronger emotionally, you can handle things with more ease.

Another technique from psychologist Dr Russ Harris, author of ‘The Happiness Trap’ is to insert the phrase “I’m having the thought that…” in front of whatever negative thought you are having. The idea being that in doing so you see your thoughts to be just a collection of words that you are telling yourself so you are able to distance yourself from them.

Calming the Storm with Meditation

You may be put off meditation, or may have tried it and found that it wasn’t enjoyable at all, or simply too difficult to quieten the mind when in so much pain. Meditation is an essential part of my personal pain management but for many new to the practice, it is difficult to still the mind and quieten that busy internal chatter of thoughts.

If you’ve never meditated before but have heard of the many benefits for chronic pain patients, physical, emotional, spiritual, and neurological, and want to begin, one way to make it easier is to use a mantra or phrase to focus on, such as that of Pema Chödrön’s quote, “You are the sky. Everything else – it’s just the weather.” Having something use as a focus on is a useful tool to train your mind to meditate with far more ease.

Meditation can be like exercise to someone [blessed with mobility] who is unfit. When start the initial exercises, it’s hard and they may be put off by this, even quit. But just as they can soon increase their fitness and work out with more ease, you too in the practice of meditation will find the thoughts do diminish with a little perseverance, and it swiftly becomes far easier to do, and crucially, more enjoyable.

Focus on the breath, breathing gently, smoothly, evenly. Simply repeat that mantra or another phrase that is soothing to you. It could be “I am here, I am still”, or a single word, like “calm”, in your mind, as you sit or lie down if sitting is not physically possible or too painful, in stillness. It helps in the learning stages to use meditative aids, such as using soothing music, low lighting, or scenting the room with some essential oil or incense. Find what works for you and preserver, the ease does come and when it does, you’ll have added another powerful tool to your pain management kit.

Take comfort in the fact you are not alone. Handling pain at all is handling it well, and you, by virtue of being here at all, are handling it miraculously.

Handling pain at all is handling it well. #chronicpain #painsupport

Friday, 24 July 2015

Is There A Good Diet For Neuropathy?

Today's post from the ever-reliable (see link below) looks at the best dietary options if you have neuropathy. While it doesn't explain the science behind the choices, it does seem to be based on a low gluten food base and as gluten is more and more associated with nerve problems, this may be logical. It also has to be said that this sort of diet is never easy to shop for and there may also be budgetary considerations to bear in mind, however, if we're aiming for the best possible dietary self-care then the ideas here may be useful to you when compiling your shopping lists.

Quick Guide to the Best Neuropathy Diet
Posted by Editor on July 20, 2015

This Guide Describes What to Eat Throughout the Day for a Healthy Diet!

You have no doubt heard that changes to your diet and lifestyle can have a tremendous impact on your health as far as neuropathy and chronic pain is concerned.

But what is a neuropathy diet? Exactly what you should be eating, and what should you avoid?

Here is a breakdown of a typical day’s worth of snacks and meals on the neuropathy diet to give you an idea of what kind of adjustments you should be making on your own.

Of course, you may need to modify this general outline for your own symptoms or pain level under the supervision of your NeuropathyDR Clinician.

First, be sure to have breakfast every morning. Ideally, eat a small amount of protein within a few minutes of waking up, which helps to jump-start your mental state as well as your metabolism.

You could have a protein shake made with vegetable protein powder (dairy-free) and coconut milk or almond milk. Or if you prefer not to drink your breakfast, try granola (gluten-free) or steel cut oats.

Next, you’ll want to have a small low-carb snack about three hours after breakfast. Half an apple or banana would do the trick or a small amount of nuts, such as almonds. Be careful when consuming packaged snacks, such as protein bars, as many of them contain a great deal of sugar.

For lunch, you’ll want more protein and veggies. The easiest way to do this is make a salad featuring your favorite kinds of greens—spinach is great. Add a small amount of chicken, tuna, turkey, or salmon for a lean protein, or use tofu if you’re vegan. Throw in a few walnuts or almonds and a drizzle of olive oil.

Have another snack in mid-afternoon, something small and low-carb like your morning snack.

For dinner, emphasize vegetables like asparagus, beets, squash, sweet potatoes, or cooked spinach. Avoid starchy veggies like white potatoes or rice. For a protein, try locally sourced hormone-free beef or fresh fish.

In the evening, have one more small snack. This time it can be a treat, such as one square of dark chocolate or a SMALL serving of gluten-free low-carb cookies.

You’ll also want to have lots of water throughout the day, and limited amounts of tea or coffee are okay.

You’ll notice that this diet is dairy-free, very low in sugar, and contains no bread products or junk food.

Try making a gradual shift into the NeuropathyDR diet over a period of a few days. You won’t believe how much better it makes you feel!

For more information on the neuropathy diet and other neuropathy basics, see our guide I Beat Neuropathy!

Thursday, 23 July 2015

Conclusions About Effectiveness Of Neuropathy Drugs

Today's post from (see link below) takes a look at the drugs currently used to control neuropathic pain and comes to conclusions which most of us concluded years ago - the drugs are not particularly effective at all but maybe they're better than nothing! The author also questions drug trials and the reporting of such, hinting that there are often hidden agendas behind the publication of results and that trial study numbers can also be misleading. You may not learn much new here but it's always interesting to read honest, expert opinion, especially when it backs up our own previously held suspicions.

The effectiveness of drugs for neuropathic pain – what do we know?
July 17, 2015 by Neil O'Connell 

Neuropathic pain (NP) – that is pain arising from identifiable damage or disease affecting the somatosensory nervous system is common and frequently severe and life-changing. It is also notoriously difficult to treat effectively. Indeed we know that for many people with NP treatment is inadequate. The International Association for the Study of Pain (IASP) have a special interest group “NeuPSIG” focused explicitly on understanding the mechanisms, assessment, prevention and treatment of NP. They have just published an up to date systematic review on the effectiveness of pharmacotherapy in Lancet Neurology. Better still it has now been made available beautifully open access. You can download it for free here.

This is a comprehensive review, containing 229 trials of the full range of pharmacological agents using robust methods, to synthesize, summarise and make value judgements about the quality of the available evidence. So what are the take home messages?

Using a primary outcome of achieving at least 50% pain relief trial outcomes were described as “generally modest”. The number of patient needed to treat with the drug compared to a placebo for one more person to achieve this outcome ranged from a relatively rosy 3.6 (95% confidence interval 3 to 4.4) for tricyclic antidepressants such as amitryptiline, 4.3 (95%CI 3.4 to 5.80 for strong opioids to a less impressive 7.2 (95%CI 5.9 to 9.21) for gabapentin, and 7.7 (6.5 to 9.4) for pregabalin (often sold under the brand-name Lyrica). It’s interesting, at least to me, how much better the older more traditional agents seem to have fared compared on effectiveness to the more modern (and commonly more expensive) agents although the safety and tolerability of gabapentin seems superior.

The spectre of publication bias also raises its head. The reviewers carefully took a number of routes to try to unpick this notoriously difficult issue and estimate that there has been overall a 10% overstatement of treatment effects. Published studies reported larger effect sizes than did unpublished studies. This is not a problem restricted to the field of pain trials. It is a burning issue across the world of clinical trials. It is very important because if we fail to base our clinical recommendations on the totality of relevant evidence (because some data are hidden from us) we are in danger of mis-estimating the benefits and the harms and as a result patients are put at risk. If you think that is pretty important then there are ways that you can help. Check out the All-Trials campaign.

Overall what does this mean? Many drugs are effective but not as effective as we would wish them to be. No pharmacological agent really impresses and for any drug the most probable outcome is failure to produce 50% pain relief. There are various potential reasons for this. The first is that the drugs may only be moderately or marginally effective, another is that neuropathic pain includes quite a mixed bag and our ability to accurately diagnose and to target drugs to specific mechanisms in the clinic is currently fairly poor.

The NeuPSIG review team formulate a number of recommendations for revision of their clinical guideline for managing NP pain, balancing the benefits, harms, costs and strength of the evidence:
a strong recommendation for use and proposal as a first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin;
a weak recommendation for use and proposal as a second line treatment for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only.

Neil O’Connell

As well as writing for Body in Mind, Dr Neil O’Connell, (PhD, not MD) is a lecturer and researcher in the College of Health and Life Sciences (Department of Clinical Sciences) at Brunel University London, UK. He divides his time between research and training new physiotherapists and previously worked extensively as a musculoskeletal physiotherapist.

He also tweets! @NeilOConnell

Neil’s main research interests are chronic low back pain and chronic pain more broadly with a focus on evidence based practice. He has conducted numerous systematic reviews and is a member of the editorial board of the Cochrane Collaboration’s Pain Palliative and Supportive Care Group (PaPaS). He also makes a mean Yorkshire pudding despite being a child of Essex. Link to Neil’s published research here. Downloadable PDFs here.

Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol.

Wednesday, 22 July 2015

Useful Video Description Of Neuropathy (Vid)

Today's post is a YouTube video about neuropathy presented by Dr. Larry Santora. He interviews Dr Shokrae, a neurologist, who gives a general description of neuropathy, with special emphasis on alcoholic neuropathy and also demonstrates the main testing procedure. He does mention some of the commonest causes but fails to mention that there are actually over 100 forms of neuropathy and over 100 causes. That said, did you know that world-wide, the commonest cause of neuropathy is leprosy? Otherwise, the interview contains some useful information, even for experienced neuropathy patients.

Peripheral neuropathy: Burning and numbness in hands, legs and feet
Dr. Larry Santora Published on 21 Apr 2013

Peripheral neuropathy is an uncomfortable burning or numbing sensation in the feet and legs. The most common causes? First is diabetes, and the second is alcohol consumption. Neurologist Amir Shokrae, M.D., explains the causes and symptoms and demonstrates the instruments used for detection of this painful condition.

Shokrae is joined by Larry Santora, M.D., medical director of the Orange County Heart Institute and host of "Health Matters with Dr. Larry Santora" television series, which airs weekly on PBS OC. Visit

Produced by Chapman University's Panther Productions, "Health Matters with Dr. Larry Santora" is sponsored by St. Joseph Health, St. Joseph Hospital, Biotronik, Churm Media, The Widdicombe Family, Medtronic, Weaver Health Solutions and Abbott Vascular.

Tuesday, 21 July 2015

Antibiotic Side Effects Include Neuropathy (Vid)

Today's post from (see link below) is a video with transcript of a news report on fluoroquinolone antibiotics such as Cipro and Levaquin (amongst others). The warning is clear and has been highlighted several times on this blog, yet these antibiotics are still routinely issued in their millions every day across the world. Be warned; if you're susceptible to, or already have neuropathic symptoms, it may be best to stay well clear of these antibiotics. At the very least, a serious discussion with your doctor may be necessary - there are always alternatives.

Thousands of adverse reactions reported from common antibiotics
Patients claim they were not properly warned of side effects from Levaquin, Ciprofloxacin

Author: Haley Hernandez, Reporter Published On: Apr 13 2015

video platformvideo managementvideo solutionsvideo player

HOUSTON - Less than a year ago, David Crain, a healthy and vibrant 33-year-old musician and personal trainer, was in the prime of his life. “I was running 6 miles in the August heat with my shirt off, screaming, yelling, listening to music effortlessly,” he said. Now, he can barely play his guitar.

Just about all I can do. It's hurting. If I do it now, I'll pay for it later,” Crain said.

Last June Crain went to the emergency room for what doctors believed was colitis. He was prescribed the antibiotic Ciprofloxacin, a generic form of Bayer’s Cipro, and began taking the recommended dosage.

“I think around about day seven or day eight, I just noticed like every time I would stand up I’d just be super-fatigued,” Crain said. “My ears rang all the time, I had trouble walking in the second month. My shoulders hurt, my tendons hurt.”

Tammy Renzi was prescribed the antibiotic Levaquin for a sinus infection. Six days into her 10-day dosage, she said she knew something wasn't right.

“I had a heaviness in my thighs. I had pressure in my lower spine. My vertebrae felt like they were rubbing on each other and I could hear the snapping in them,” Renzi said.

Both Crain and Renzi are not alone. From November 1997 to May 2011, more than 85,000 adverse reactions to Levaquin were reported to the Food and Drug Administration, including 1,174 deaths.

More than 67,000 adverse reactions to Cipro were also reported, including 1,257 deaths.

Dr. Charles Bennett, state chair of Medication Safety at the University of South Carolina, has been tracking the issue. He said Crain and Renzi's reactions may be caused by a mysterious genetic predisposition.

“Research should be done to identify those genetic factors,” Bennett said. “You certainly wouldn't want to take a drug if you knew you had a genetic predisposition to its side effects.”

Until that research is done, Bennett has petitioned the FDA, requesting stronger warnings.

“The current insert has a black box warning for tendon rupture and neurologic damage. It needs to be beyond the package insert,” he said.

Channel 2 Investigates reached out to both drug manufacturers.

According to Bayer Corporation, the FDA issued a drug safety communication requiring that "the drug labels and medication guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect of peripheral neuropathy."

Johnson & Johnson, Levaquin’s parent company, wrote, “Since 2004, the Levaquin label has informed physicians and patients about possible side effects related to peripheral neuropathy.”

Crain and Renzi said they want everyone to know the risks so that they don't end up with the same fate.

“I wouldn't take it again if my life depended on it,” Renzi said.

“My biggest fear is that I’m, you know, my son is never going to know who I was,” Crain said.

Renzi and Crain are not currently considering legal action, but in 2012 Johnson & Johnson settled lawsuits with 845 plaintiffs who claimed they were not properly warned about the risks.

Monday, 20 July 2015

Is Antidepressant Milnacipran Any Good For Neuropathy?

Today's post from (see link below) looks at Milnacipran, an antidepressant and asks whether it's effective in reducing neuropathic pain. Due to antidepressants and especially SNRI (serotonin–norepinephrine reuptake inhibitor) antidepressants, being standard treatment for neuropathic pain, that doesn't mean to say that every antidepressant in the range is effective. Cochrane has looked at the drug and concludes that there is no evidence to suggest Milnacipran is of any help in taming nerve pain. Forewarned is forearmed as they say, so if your doctor suggests taking Milnacripan, it may be worth presenting this evidence to him or her.

Milnacipran for neuropathic pain in adults
Authors: Derry S, Phillips T, Moore R, Wiffen PJ Published: 6 July 2015

Neuropathic pain is pain coming from damaged nerves. It is different from pain messages that are carried along healthy nerves from damaged tissue (for example, a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines to those used for pain from damaged tissue. Medicines such as paracetamol or ibuprofen are not usually effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain.

Milnacipran is an antidepressant, and antidepressants are widely recommended for treating neuropathic pain; milnacipran may also be useful in these painful conditions.

This is an update of a review of milnacipran for neuropathic pain and fibromyalgia, first published in 2012. That review has been split so that this one looked only at neuropathic pain, and a separate review looks at fibromyalgia.

In February 2015 we performed searches to look for clinical trials where milnacipran was used to treat neuropathic pain in adults.

We found only a single, small study of 40 participants who had chronic low back pain with a neuropathic component. Milnacipran was no different from placebo in terms of pain or adverse events (very low quality evidence).

There was no evidence to support use of milnacipran to treat neuropathic pain conditions.

Authors' conclusions:

There was no evidence to support the use of milnacipran to treat neuropathic pain conditions. 


Milnacipran is a serotonin–norepinephrine reuptake inhibitor (SNRI) that is sometimes used to treat chronic neuropathic pain and fibromyalgia. This is an update of an earlier review of milnacipran for neuropathic pain and fibromyalgia in adults originally published in The Cochrane Library Issue 3, 2012. We split that review so that this one looked only at neuropathic pain, and a separate review looks at fibromyalgia. 


To assess the analgesic efficacy and associated adverse events of milnacipran for chronic neuropathic pain in adults. 

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to 23 February 2015, together with reference lists of retrieved papers and reviews. 

Selection criteria:

We included randomised, double-blind studies of eight weeks' duration or longer, comparing milnacipran with placebo or another active treatment in chronic neuropathic pain. 

Data collection and analysis:

Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any analysis. 

Main results:

We included a single study of 40 participants with chronic low back pain with a neuropathic component. It found no difference in pain scores between milnacipran 100 mg to 200 mg daily or placebo after six weeks (very low quality evidence). Adverse event rates were similar between treatments, with too few data to draw conclusions (very low quality evidence).

Sunday, 19 July 2015

New And Exciting Stem Cell Therapy For Neuropathy

Today's post from (see link below) is another article proclaiming the latest 'breakthrough' in neuropathy treatment. Don't worry, it's not a lurid advertisement from yet another questionable neuropathy clinic but shows the results of new research on stem-cell therapy. If you read it, you may justifiably get excited at the prospect of a pain-free existence thanks to bone marrow cell injections but this sort of treatment on humans is a long way off and as such can be frustrating information for many neuropathy patients. Nevertheless, the field of stem-cell therapy is beginning to show multiple promising results and as such makes interesting reading and gives hope for the future.

‘Amazing’ New Stem Cell Treatment for Neuropathy
By Pat Anson, Editor July 13, 2015

Researchers at Duke University say an experimental stem cell therapy being tested on animals shows great potential to provide long-lasting pain relief for people suffering from diabetic neuropathy or other types of nerve damage.

In a study published in the Journal of Clinical Investigation, researchers said mice injected with a type of stem cell known as bone marrow stromal cells (BMSCs) were much less sensitive to nerve pain.

"This analgesic effect was amazing," said Ru-Rong Ji, PhD, a professor of anesthesiology and neurobiology in the Duke School of Medicine. "Normally, if you give an analgesic, you see pain relief for a few hours, at most a few days. But with bone marrow stem cells, after a single injection we saw pain relief over four to five weeks."

BMSCs are known to produce an array of healing factors and can be coaxed into forming other types of cells in the body. They are already being used to treat people with serious burns, inflammatory bowel disease, heart damage and stroke.

"Based on these new results, we have the know-how and we can further engineer and improve the cells to maximize their beneficial effects," said Ji.

Researchers injected the mice with stem cells through a lumbar puncture, infusing them into the fluid that bathes the spinal cord.

The picture on the right shows how the injected stem cells (in red) migrated to the site of the nerve injury and were still present four weeks after treatment.

A molecule emitted from the injured nerve cells -- which has previously been linked to neuropathic pain – is believed to act as a “homing signal” and attract the stem cells.

Researchers measured levels of anti-inflammatory molecules in the mice and found that one in particular, TGF-β1, was present in higher amounts in the spinal fluid of the stem cell-treated animals.

TGF-β1 is a protein that is secreted by immune cells and is common throughout the body. Research has shown that people with chronic pain have too little TGF-β1.

Injecting TGF-β1 directly into spinal cord fluid provides pain relief, but only for a few hours, according to Ji. By contrast, bone marrow stromal cells stay on site for as much as three months after the infusion.

Ji’s research team is working to identify stem cells that produce more TGF-β1, as well as other types of pain relieving molecules. In addition to diabetic neuropathy, researchers believe stem cell therapy could also be used to treat pain from chemotherapy, surgical amputation, lower back pain and spinal cord injuries.

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association. Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients feel pain or loss of feeling in their toes, feet, legs, hands and arms. It may also include a persistent burning, tingling or prickling sensation. The condition can lead to injuries, chronic foot ulcers and even amputations.

Another recent animal study by researchers in the U.S. and South Korea found that diabetic rats given intramuscular injections of bone marrow stromal cells experienced both angiogenesis (blood vessel growth) and a restoration of the myelin sheath -- a protective covering over nerve cells damaged by neuropathy.

"Currently, the only treatment options available for DN (diabetic neuropathy) are palliative in nature, or are directed at slowing the progression of the disease by tightly controlling blood sugar levels," said Dr. John Sladek, Jr., Professor of Neurology, Pediatrics, and Neuroscience, Department of Neurology at the University of Colorado School of Medicine.

"This study offers new insight into the benefits of cell therapy as a possible treatment option for a disease that significantly diminishes quality of life for diabetic patients.”

The study is being published in the journal Cell Transplantation.

Saturday, 18 July 2015

Alcohol And Nerve Damage: Not To Be Underestimated.

Today's post from (see link below) looks at a widely underestimated cause of nerve damage and neuropathic complications and that is alcohol. Most people are well aware of the results of over-indulging in alcohol but may not be aware what it can do to your nervous system and neurological functions. This article looks at what it is, what the symptoms are and how it is treated, with the conclusion that like most forms of neuropathy, there is no cure. Once the damage is done, you're left with trying to control the symptoms. It also goes without saying that if you already have neuropathy, alcohol may help you temporarily forget but will only worsen the condition in the long run. Everything in moderation folks!

 Alcoholic Neuropathy – Symptoms, Causes and Treatment
17 Jul, 2015

As Dr. Siwek mentions in this week’s episode of the Pain Channel, April is Alcohol Awareness Month. When we think of alcohol awareness, the first things that pop into our minds are drunk driving, designated drivers, and sobriety tests, right? Popular culture has taught us to correlate drinking with driving consequences. But Alcohol Awareness Month is truly about the health consequences associated with alcoholism such as neurologic complications, vitamin deficiencies, liver disease, and much more.

Neurologic complications of alcohol abuse may also result from nutritional deficiency, because alcoholics tend to eat poorly and may become depleted of thiamine or other vitamins important for nervous system function. Persons who are intoxicated are also at higher risk for head injury or for compression injuries of the peripheral nerves. Sudden changes in blood chemistry, especially sodium, related to alcohol abuse may cause central pontine myelinolysis, a condition of the brainstem in which nerves lose their myelin coating. Liver disease complicating alcoholic cirrhosis may cause dementia, delirium, and movement disorder.

What is Alcoholic Neuropathy?

Alcoholic neuropathy, also known as alcoholic polyneuropathy, is the direct result of overconsumption of alcohol over extended periods of time. Unfortunately, alcoholics to not eat right, nor exercise, so their bodies slowly become deficient in several nutritional areas. There is a continual debate over whether it is the alcohol itself, or malnutrition that accompanies alcoholism, which is the root cause of alcoholic neuropathy.

The causes of alcoholic neuropathy are extensive, from irregular lifestyles leading to missed meals and poor diets, to a complete loss of appetite, alcoholic gastritis, constant vomiting, and damaging of the lining of the gastrointestinal system. All of these symptoms cause nutritional deficiencies, and when the lining of the gastrointestinal system becomes compromised, the body is not able to absorb the proper nutrients.

Alcohol consumption in extremes can also increase the toxins within a person’s body such as ethanol and acetaldehyde, which many believe are directly linked to alcoholic neuropathy.

What are the Symptoms of Alcoholic Neuropathy?

In most cases, alcoholic neuropathy sets gradually into the body so that the individual does not realize they have this condition until it is deeply rooted within their system. While weight loss is an early warning sign, it is also a side effect of heavy drinking, so most individuals with alcohol conditions do not realize what their body is trying to tell them. Painful paralysis and motor loss is the first symptom that individuals tend to truly take notice of. According to, the following is a list of possible symptoms of alcoholic neuropathy:

Normal symptoms can include:

loss of sensation
tingling in the feet/hands
weak ankles
weakened muscles and a burning feeling in the feet.

Gastrointestinal symptoms can include:

loose bowel movements
feelings of nausea, possibly vomiting and constipation.

Men may experience:

the inability to hold liquid (incontinence)
and even impotence in some cases.

In severe occurrences of alcoholic neuropathy:

the autonomic nerves are damaged
autonomic functions are involuntary, like the heart beat and respiration.

Because this chronic condition effects the brain and nerves, pain can be intense and constant, sharp and quick, or dull and prolonged, and cramping may occur in muscles without warning.

Treatment of Alcohol Neuropathy

Most pain doctors in Arizona will tell you that there is no known cure for alcohol neuropathy, but there are successful pain management and treatment methods to help patients get back into life. At this point, when a patient has been diagnosed with alcohol neuropathy, a pain doctor’s best intention is to control the pain. Once that damage has been done from this chronic condition, unfortunately it cannot be undone. However, the pain can be controlled.

Obtaining from alcohol consumption will be the pain doctor’s first course of treatment. Whether it’s through counseling, Alcoholic’s Anonymous meetings, or in-house psychological evaluations, kicking the habit is the first step. This will be the toughest step for anyone living with alcohol neuropathy.

Next, your pain doctor will want to manage your nutritional intake through medication and a strict diet. Using a multidisciplinary team of industry experts, your pain doctor will no doubt sit you down with a nutritionist to determine the best course to get you back on track with a healthy diet. Multivitamins are also a key aspect in nourishing your body.

Physical therapy is usually called for in cases of alcohol neuropathy due to the great damage that has been done to the nerves. Since motor loss is a symptom of this chronic condition, your pain doctor will want to bring blood flow and life back into the affected areas of your body. One of the best ways to do this is through exercise and physical therapy.

Most individuals who abuse alcohol are also at great risk for abusing pain medication while going through pain management treatment, which is always a concern for pain doctors in Arizona. According to NYTimes Health, the least amount of medication needed to reduce symptoms is advised, to reduce dependence and other side effects of chronic use.

Common medications may include over-the-counter analgesics such as aspirin, ibuprofen, or acetaminophen to reduce pain. Stabbing pains may respond to tricyclic antidepressants or anticonvulsant medications such as phenytoin, gabapentin, or carbamazepine.

While it’s deemed impossible to reverse the damage already done to the body’s nerves, pain doctors can help patients living with alcoholic neuropathy reduce and control pain and get back into life. Of course, the best way to prevent this chronic condition is to respect your alcohol intake, but if you are suffering from this debilitating condition speak immediately to an Arizona pain specialist about your options at

Friday, 17 July 2015

Gluten Intolerance And Neuropathic Disorders

Today's long post from (see link below) is a highly complex one examining the evidence for neurological damage as a result of gluten intolerance. Apologies that it's not an article you can read quickly over the breakfast table but occasionally these complex papers are necessary for people who want meat on the bones of a subject. There's no doubt that gluten intolerance is a bit of a hot topic on the neuropathy discussion forums, mainly because nobody wants to believe it and have to radically alter their diets but it may just be true for an awful lot of people. Even if you just scan this article, you will get the gist of why gluten plays a significant role in the workings of the nervous system.

Gluten sensitivity as a neurological illness
M Hadjivassiliou, R A Grünewald, G A B Davies-Jones

J Neurol Neurosurg Psychiatry 2002;72:560-563 doi:10.1136/jnnp.72.5.560
Gluten sensitivity
+ Author Affiliations
Department of Neurology, The Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK
Correspondence to:
 Dr M Hadjivassiliou, Department of Neurology, The Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK;

From gut to brain

It has taken nearly 2000 years to appreciate that a common dietary protein introduced to the human diet relatively late in evolutionary terms (some 10 000 years ago), can produce human disease not only of the gut but also the skin and the nervous system. The protean neurological manifestations of gluten sensitivity can occur without gut involvement and neurologists must therefore become familiar with the common neurological presentations and means of diagnosis of this disease.


” . . .the stomach being the digestive organ, labours in digestion, when diarrhoea seizes the patient . . .and if in addition, the patient's general system be debilitated by atrophy of the body, the coeliac disease of a chronic nature is formed”.1

This extract is from the book on chronic diseases by Aretaeus the Cappadocian, one of the most distinguished ancient Greek doctors of the first century AD. This chapter, entitled “on the coeliac diathesis”, was the first description of coeliac disease (from the greek word for abdominal). Aretaeus' books were first published in Latin in 1500 and the new Latin word coeliac was used to translate κ⊝ιλιακη. Coeliac disease (CD) remained obscure until 1887 when Samuel Gee gave a lecture entitled On the coeliac affection2 at the Hospital for Sick Children, Great Ormond Street, London. In it he acknowledged Areteaus' contribution and went on to give an accurate description of CD based on his own clinical observations.

With clinical manifestations primarily confined to the gastrointestinal tract or attributable to malabsorption, it was logical to assume that the target organ and hence the key to the pathogenesis of this disease was the gut. The first report of neurological manifestations associated with CD was by Carnegie Brown in 1908.3 In his book entitled Sprue and its treatment he mentioned two of his patients who developed “peripheral neuritis”. Elders reported the association between “sprue” and ataxia in 1925.4 The validity of these and other such reports before 1960 remains doubtful given that a precise diagnosis of CD was not possible before the introduction of small bowel biopsies.

The treatment of CD remained empirical until 1940–50 when the Dutch paediatritian Willem Dicke noted the deleterious effect of wheat flour on children with CD.5 Removal of dietary products containing wheat was shown to result in complete resolution of the gastrointestinal symptoms and a resumption of normal health. The introduction of the small bowel biopsy in 1950–60 confirmed the gut as a target organ. The characteristic features of villous atrophy, crypt hyperplasia and increase in intraepithelial lymphocytes with improvement while on gluten-free diet, became the mainstays of the diagnosis of CD. In 1961 Taylor published an immunological study of CD.6 In his paper he commented that “ . . .an obstacle to the acceptance of the immunological theory of causation has been the lack of satisfactory demonstration of antibodies to the protein concerned”. He went on to demonstrate the presence of circulating antibodies against gliadin (antigliadin antibodies), the protein responsible for CD. This provided further evidence that CD was immunologically mediated and that the immune response is not confined to the mucosa of the small bowel. Antigliadin antibodies became a useful screening tool for the diagnosis of CD.

In 1966, Marks et al demonstrated an enteropathy in nine of 12 patients with dermatitis herpetiformis,7 an itchy vesicular skin rash mainly occurring over the extensor aspect of the elbows and knees. The enteropathy had a striking similarity to that seen in CD. It was later shown that the enteropathy and the skin rash were gluten dependent but skin involvement could occur even without histological evidence of gut involvement. This was the first evidence that the gut may not be the sole protagonist in this disease.


In 1966 Cooke published a landmark paper on 16 patients with neurological disorders associated with adult CD.8 This was the first systematic review of the subject after the introduction of diagnostic criteria for CD. Ten of these patients had a severe progressive neuropathy. All patients had gait ataxia and some had limb ataxia. Neuropathological data from postmortem examinations showed extensive perivascular inflammatory changes affecting both the central and peripheral nervous systems. A striking feature was the loss of Purkinje cells with atrophy and gliosis of the cerebellum. All 16 patients had evidence of severe malabsorption as evidenced by anaemia and vitamin deficiencies as well as profound weight loss.

Several case reports followed, primarily based on patients with established CD, often with persisting troublesome gastrointestinal symptoms followed by neurological dysfunction. Data from patients with CD presenting with gastrointestinal symptoms followed up in a gastrointestinal clinic suggest that otherwise unexplained neurological dysfunction is a complication in 6% to 10% of cases.9

A review of all such reports (with biopsy proved CD) from 1964 to date shows that ataxia and peripheral neuropathy are the commonest neurological manifestations seen in patients with established CD (table 1). Less common manifestations include inflammatory myopathies10 and myoclonic ataxia.11 Isolated dementia is uncommon and most cases tend to have additional neurological features (for example, ataxia or neuropathy). Patients with epilepsy associated with occipital calcifications on CT and CD have been described,12 mainly in Italy. Most present with epilepsy in childhood. Such cases are rare in the United Kingdom.

Neurology of coeliac disease (based on a review of 35 papers of single or multiple case reports from 1964 to 2000)


Some studies looking at normal populations have shown that the prevalence of CD is much higher than previously thought13,14 (approximating to 1 in 100). Most of such patients have no gastrointestinal symptoms. In addition, experimental data in patients with gluten sensitivity suggest that there is a range of mucosal abnormalities affecting the small bowel ranging from preinfiltrative (histologically normal) to infiltrative, to hyperplastic to flat destructive (seen in CD), and finally to the irreversible hypoplastic atrophic lesions.15 Increasing the gluten load may result in progression of the severity of the lesion. In those patients where the histology is normal, staining of the T cell subpopulations of the intraepithelium of the small bowel biopsies shows alteration of T cell subpopulations of the intraepithelial lymphocytes (increase of the γ/δ T cells). This finding is said to be a marker of potential CD.16 This procedure is only available in a very few pathology laboratories, rendering its use limited.

Finally, CD has a very strong association with the human lymphocyte antigen (HLA) of the major histocompatibility complex. Ninety per cent of patients with CD have the HLA DQ2; the rest have DQ8.

These advances suggest that gastrointestinal symptoms are absent in most patients with CD, that the definition of gluten sensitivity can no longer be solely based on the presence of an enteropathy and that genetic susceptibility may be an important additional marker for gluten sensitivity. Given the knowledge of these advances and approaching gluten sensitivity from a neurological perspective we set up to address the following question: Does cryptic gluten sensitivity play a part in neurological illness?


Over the past 8 years we have used antigliadin antibodies to screen patients with neurological dysfunction of unknown aetiology. Our original study concluded that gluten sensitivity played an important part in neurological illness.17 The evidence was statistical: Patients with neurological disease of unknown aetiology were found to have a much higher prevalence of circulating antigliadin antibodies (57%) in their blood than either healthy control subjects (12%) or those with neurological disorders of known aetiology (5%). Since then we have identified 131 patients with gluten sensitivity and neurological disorders of unknown aetiology. Table 2 shows the neurological diagnoses we have encountered. Perhaps not surprisingly the commonest manifestations are ataxia (also known as gluten ataxia18) and peripheral neuropathy.19


Systematic screening of 143 patients with so-called “idiopathic sporadic ataxia” showed that 41% had gluten sensitivity as defined by the presence of circulating antigliadin antibodies20 (IgG with or without IgA). The prevalence of antigliadin antibodies in 51 patients with familial ataxia did not differ from that found in normal healthy control subjects (13%). The mean age of onset of the ataxia was 54 but we have recently seen three patients with early onset (under 20 years of age) sporadic idiopathic ataxia and gluten sensitivity. Recently four patients have been described with CD presenting as gait disturbance and ataxia in infancy.21 Alhough the ataxia tends to be slowly progressive, in some cases it can take a very rapid course with the development of cerebellar atrophy within a year of the onset of the illness (fig 1). Ataxia and myoclonus is a much less common presentation (only four patients in these series). We have encountered two patients who in addition to ataxia had evidence of chorea but normal genetic testing for Huntington's disease. Gluten ataxia primarily affects the lower limbs and gait. Extrapyramidal or autonomic features are rarely apparent and these features distinguish it from the cerebellar variant of multisystem atrophy (MSA). Screening of patients with clinically probable MSA (cerebellar variant) for the presence of antigliadin antibodies showed the prevalence to be similar to the normal population. Brain MRI usually shows cerebellar atrophy; sometimes with evidence of white matter abnormalities. Up to 40% of patients also have a sensorimotor axonal peripheral neuropathy that can often be subclinical. In a few cases oligoclonal bands are present in the CSF.


Peripheral neuropathy is the second commonest manifestation of gluten sensitivity. Prospective screening of 101 patients with idiopathic peripheral neuropathy has shown the prevalence of gluten sensitivity to be 40% (unpublished data). The commonest type of peripheral neuropathy we encountered is sensorimotor axonal (26) followed by mononeuropathy multiplex (15), pure motor neuropathy (10), small fibre neuropathy (four) and mixed axonal and demyelinating (two). The neuropathy is usually chronic and of gradual progression. Patients with a pure motor neuropathy may progress to involvement of sensory fibres.


We encountered eight patients with myopathy and gluten sensitivity. Three had an additional neuropathy. Muscle biopsy showed inflammatory changes in five. One patient had evidence of inclusion body myositis. One patient had low concentrations of vitamin D and a predominantly proximal myopathy.

Myelopathy is rare in our series and was only seen in two patients.

We have recently identified a subgroup of patients with gluten sensitivity who complained of episodic severe headache often with transient neurological deficit and extensive white matter abnormalities on MRI.22 Some of them also had ataxia or neuropathy. Their headache resolved with the introduction of a gluten free diet though the MRI abnormalities persisted at least for the short follow up period. We have also found a higher incidence of gluten sensitivity in patients with systemic vasculitis and neurological involvement, perhaps reflecting the autoimmune nature of gluten sensitivity. There is a well known association of CD with other autoimmune diseases23 (for example, diabetes, thyroid disease). This may account for the finding of the presence of antigliadin antibodies in all four of our patients with stiff-person syndrome.

Some researchers think that prolonged exposure to gluten in a gluten sensitive person may be the trigger for the development of other autoimmune disease.23

”But antigliadin antibodies lack specificity”

IgG anti-gliadin antibodies have been the best diagnostic marker in the neurological population we have studied. IgG anti-gliadin antibodies have a very high sensitivity for CD but they are said to lack specificity. In the context of a range of mucosal abnormalities and the concept of potential CD, they may be the only available immunological marker for the whole range of gluten sensitivity of which CD is only a part. Further support for our contention comes from our HLA studies. Within the group of patients with neurological disease and gluten sensitivity (defined by the presence of anti-gliadin antibodies) we have found a similar HLA association to that seen in patients with CD: 70% of patients have the HLA DQ2 (30% in the general population), 9% have the HLA DQ8, and the remainder have HLA DQ1. The finding of an additional HLA marker (DQ1) seen in the remaining 20% of our patients may represent an important difference between the genetic susceptibility of patients with neurological presentation to those with gastrointestinal presentation within the range of gluten sensitivity.

”But antigliadin antibodies have been superseded by anti-endomysial and transglutaminase antibodies”

The introduction of more CD specific serological markers such as anti-endomysium and more recently transglutaminase antibodies may have helped in diagnosing CD but their sensitivity as markers of other manifestations of gluten sensitivity (where the bowel is not affected) is low. This certainly reflects our experience with patients with gluten sensitivity who present with neurological dysfunction. Endomysium and transglutaminase antibodies are only positive in the majority but not in all patients who have an enteropathy. Patients with an enteropathy represent only a third of patients with neurological manifestations and gluten sensitivity. Antigliadin antibodies unlike endomysium and transglutaminase antibodies are not autoantibodies. They are antibodies against the protein responsible for gluten sensitivity.
“What do I do with a patient with positive anti-gliadin antibody test but normal duodenal biopsy”

Only one third of the patients with neurological disorders associated with gluten sensitivity have villous atrophy on duodenal biopsy. Even some with biochemical markers of malabsorption such as low serum vitamin B12, low red cell folate, or vitamin D concentrations had normal conventional duodenal histology.17 These cases may illustrate the patchy nature of bowel involvement in coeliac disease and the inaccurate interpretation of duodenal biopsies by inexperienced histopathologists. Preliminary data based on staining of the subpopulation of T cells in the small bowel epithelium suggests that these patients have potential CD.24 There are, however, patients where the immunological disorder is primarily directed at the nervous system with little or no damage to the gut. Our practice is to offer a gluten-free diet to these patients unless the HLA genotype is not consistent with susceptibility to gluten intolerance (that is, other than HLA DQ2, DQ8, or DQ1). All patients are followed up and any clinical response is documented. 

”But my patient has not responded to a gluten free diet”

Reports in the literature of the effect of the gluten-free diet on neurological dysfunction are conflicting. Almost all patients reported in the literature have the diagnosis of CD before the development of neurological dysfunction. They may represent a different group of patients from those presenting with neurological dysfunction without bowel involvement. Additionally, improvement of gastrointestinal symptoms and improvement of the histological abnormalities on repeat small bowel biopsy often were the measures used to assess the response to the diet. Serological evidence of response (for example, sustained elimination of antigliadin antibodies) has rarely been used as confirmation of strict adherence to the gluten-free diet. Incomplete elimination of gluten from the diet may be enough to abolish gastrointestinal symptoms with recovery of the small bowel mucosa but is insufficient to arrest the state of heightened immunological responsiveness resulting in neuronal injury. There is a group of patients with CD “resistant” to gluten-free diet. This may reflect hypersensitivity to the minute amounts of gluten present in most “gluten-free” products. An analogous situation may exist in cases of gluten ataxia or gluten related neuropathy. The monitoring of neurological improvement in such cases is made difficult by the slow and sometimes incomplete regeneration of the nervous system. In cases of gluten ataxia where the underlying pathology is loss of Purkinje cells, one may only expect the stabilisation of the disease without any definite clinical improvement. This is in marked contrast to the response seen in patients with florid gastrointestinal symptoms who notice almost immediate improvement after the introduction of a gluten-free diet.

“Isn't the neurological damage nutritional?”

Nutrient deficiencies (B12, folate, vitamin D, vitamin E) are rare in this neurological population. Given that two thirds of these patients have no enteropathy this is hardly surprising. The concept of the neurological manifestations being nutritional in origin is now outmoded. Intestinal mucosal damage in coeliac disease is the result of both humoral and T cell mediated inflammation. Such inflammation is not, however, confined to the gut, as activated HLA restricted gliadin specific T cells25 and antigliadin antibodies are found systemically. Antigliadin antibodies are also found in the CSF.26 Postmortem findings from two of our patients with gluten ataxia has shown perivascular cuffing with both CD4 and CD8 cells. This inflammation was primarily seen in the white matter of the cerebellum. There was also marked but patchy Purkinje cell loss. We have also found antibodies against Purkinje cells in patients with gluten ataxia. Our research suggests that IgG antigliadin antibodies cross react with epitopes on Purkinje cells from human cerebellum.27 Characterisation of the anti-Purkinje cell antibodies by immunoblotting may provide a useful marker for the diagnosis of gluten ataxia in a manner analogous to the use of antiendomysium antibodies as a marker for coeliac disease or the anti-Yo antibody in paraneoplastic cerebellar degeneration.


Gluten sensitivity is best defined as a state of heightened immunological responsiveness in genetically susceptible people.15 This definition does not imply bowel involvement. That gluten sensitivity is regarded as principally a disease of the small bowel is a historical misconception.28 Gluten sensitivity can be primarily and at times exclusively a neurological disease.29 The absence of an enteropathy should not preclude patients from treatment with a gluten-free diet. Early diagnosis and removal of the trigger factor by the introduction of gluten-free diet is a promising therapeutic intervention. IgG antigliadin antibodies should be part of the routine investigation of all patients with neurological dysfunction of obscure aetiology, particularly patients with ataxia and peripheral neuropathy.


We are currently conducting a trial of the effect of gluten-free diet in patients with gluten ataxia and would welcome referrals of patients with sporadic idiopathic ataxia. We have received funds from SHS International and Ultrapharm Ltd towards a pilot study of the effect of gluten-free diet on patients with neurological dysfunction and gluten sensitivity and a grant from The Friedreich's Ataxia Group for research into the immunological mechanisms of the pathogenesis of gluten ataxia. 


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