Tuesday, 18 September 2018

Shingles: One Of The Most Painful Forms Of Neuropathy

Today's post from luciadavis.com (see link below) is a personal account of life with Shingles, which many of you will have heard of and many will have suffered from. It's a form of neuropathy with a definite cause - the virus Herpes Zostra (the same virus that causes Chicken pox) - and as such is often not seen as a neuropathic problem but the virus uses nerves to travel to the skin surface producing the rashes, blisters and pain you may be aware of. The virus can lie dormant in damaged nerve cells for decades without causing any symptoms. In some people, the virus wakes up and travels along nerve fibers to the skin and then you can suffer a lifetime of recurring attacks. The nerve damage is known as post-herpetic neuralgia and if you've had it, you'll know how painful it can be and this article puts that very clearly into words. Certain viral medications can help control the disease and reduce the frequency of the attacks but they are unfortunately not a cure.

Slaying the Dragon
Lucia N. Davis September 12, 2018

It’s been a while since I wrote a post. Stuff happened. More accurately: Shingles happened.

Shingles gets its own capital S. Why? Because Shingles sucks. Big time. Are there worse things than getting Shingles? Absolutely. But still, it was a miserable affair.

For those of you who haven’t made their acquaintance with Shingles, let me introduce you. It’s a reactivation of the same virus that causes chickenpox. After one recovers from the chickenpox, usually sometime during childhood, the virus does not die as one would expect. Instead, it takes a long, nice, quiet vacation somewhere within nerve tissue near the spinal cord, while we continue life, blissfully unaware of its presence.

That is, until it decides the holidays are over. Pox, apparently, is an old medieval term for curse. Ha! Well put. During a period of poor resilience the lurking virus pops up like an evil jack-in-the box, travels along a nerve to the skin and produces a localized, nasty rash, as well as a tremendous amount of pain.

I never thought about Shingles before it slithered its way in—or rather—out. Why would I? I haven’t reached the age when they start offering vaccination for it. Surely young people don’t get it, right? Wrong, unfortunately.

The chickenpox virus is a member of the Herpes family—the medical term for Shingles is Herpes Zoster.
Zoster is derived from Greek, meaning “girdle” or “belt”. Shingles’ rash looks like a belt when it’s located on the torso, as it wraps around one side. The English word “Shingles” most likely comes from the Latin word for “girdle,” which is “cingulus.” It has nothing to do with the roof of your house. Even though my six-year old kept asking me why the roof was making me sick.

Yes, why indeed? Not the roof, but why did I get Shingles? I did not feel like I was overly stressed. Yes, I was possibly chronically sleep deprived and I had just recovered from a cold, but that was not anything I hadn’t handled before. Be that as it may, the Shingles hit me hard. Sitting in the doctor’s office, my rash solicited the empathetic “Oh my, I haven’t seen it this bad in quite some time!” which no patient wants to hear ever, although I appreciated the frankness of it. It sure validated my intense discomfort. Shingles, as I discovered, can be extremely painful.

I had some time on my hands to think about this pain—that is, after I slept for a week. It’s quite amazing how many different qualities pain can have. As it turns out, Shingles is an absolute treasure trove for descriptive writing. It felt like a dragon had lodged itself in my liver, where it strangled me with its tail, while simultaneously breathing fire and stabbing me with its nails.

Shingles’ pain is relentless and exhausting, even after the skin has healed, and because it’s nerve pain, it doesn’t respond well to normal pain medication. There is something about chronic pain and having to grit your teeth the whole day. Let’s just say I was not easy to be around with. At some point the healed skin started to itch terribly as well, and upon scratching it would erupt in flames, so it was either pain, itch, or burn, or all of the above. Next time I am contemplating killing off an unlikable character in one of my books, I may just consider giving him/her Shingles instead.

So, what did I do? There’s not much you can do unfortunately. I took my anti-virals. I rested and wallowed in my misery. And I hoped it would go away—which is not a given. For some people the post-herpetic nerve pain can last a long time. I was reluctant to take any medication other than Tylenol or Ibuprofen, so I finally opted for some acupuncture. Whether it was this or just the natural course of the illness, I’ll never know, but after weeks, the pain did slowly improve. Now, three moths later, it’s more like background noise: annoying at times, but ignorable.

During all this, my website languished, as did my Facebook page. I worked on my work-in-progress, but only when I felt up to it. In the summer we took a long vacation and I focused mainly on family time, resting and maintaining a healthy life-style.

I cannot tell you how grateful I am the dragon is on its way out. Slowly withering away, it still softly claws at me every now and then, but hopefully soon it will take its last breath. And I pray it has not created any offspring to come back and find me; one visit was more than enough.


Monday, 17 September 2018

The Disturbing Truth About The Doctor/Patient Relationship In 2018

Today's lengthy but very interesting post from neurologybuzz.com (see link below) may at first sight, seem to be disconnected from neuropathy as a core subject but actually, it gets to the core of and tells the truth about how our treatment (anno 2018) as patients, has been negatively influenced by current changes in the medical systems across the world. If ever a disease required an individual approach, with individual care directly targeted at the individual nature of the patient and his/her condition...it's neuropathy. No two neuropathy patients experience the disease the same, so it's vital that doctors treat their patients as special cases that don't conform to formulaic medicinal approaches. Unfortunately, the world we live in has changed and algorithms rule! This means that doctors are tethered to budgets and systems and are not allowed to 'deviate' to suit the patient. this leads to frustration on the part of the patient, who feels neglected and not taken seriously and even more frustration for the doctor, who recognises the need for individual attention but is restricted by bureaucracy, time restraints and budgets. Both sides lose! This article outlines the problems that doctors face and how protests by both patient and doctor are silenced and ignored. Why is this important to you as a nerve pain sufferer? Because, it will be easier for you and your doctor to strike up a working relationship, if you also understand the restrictions that your doctor is facing. Letting him or her know that you understand what's going on, will lead to the doctor doing his/her best for you and let's face it...that's what we all want in the end isn't it?

Demise of medicine: neurologist who advocated for patients is silenced 
Virginia Thornley, M.D., Neurologist @VThornleyMD
July 30, 2018 https://neurologybuzz.com/  


Many physicians are overwhelmed by patient loads, 10 minute visits, the wealth of documentation dictated by health insurance requirements and the overwhelming overtaking of medicine by non-physician personnel. Wellness programs abound but this only addresses the symptoms of the underlying problem. We see articles and articles abounding online: physician fired or coerced into resignation for speaking about the quality of healthcare placing profits over patients or speaking about non-physicians overstepping boundaries putting patients at risk. Physicians are termed “non-team players” and “disruptors.” We see non-physicians calling themselves doctors when they are not doctors of medicine but something else other than medicine managing the most complex cases in the hospital setting at times performing duties beyond their limits. NP’s and PA’s see patients, order tests and make decisions on treatment. This is most rampantly seen on the primary care horizon under the liability and license of a physician. Some aggressive organizations of NP’s are now very powerful seeking independent practice, meaning practicing without the supervision of a physician. They have a place in medicine but their positions were never designed to overtake the skill sets of physicians. Patients are referred in-network in order to increase profitability of that company even when a better physician may be outside of the network. Appointments, which used to be at the discretion of the physician, are now reduced to staring at a computer making sure all the boxes are clicked rather than looking at the patient in the eye to construct their stories. The cancer is the business model at the center which must be ripped out. The minute medicine became profit-centered and not patient-centered was the beginning of the end of healthcare as we knew it. This is the healthcare we face today.

The training of a medical physician

Previously, the connection was straightforward-physician and patient. That connection is sacred which nobody on this earth held, it is that sacred. https://neurologybuzz.com/2018/06/06/returning-to-the-sacred-relationship-between-patient-and-physician/ A physician’s duty is towards the patient, taking care of them using all the knowledge of the sciences with which they trained for so long. There are 4 years of pre-medical school, 4 years of medical school, 1 year of internship, 3-5 years of residency training and 2-3 years of fellowship. That is 11-17 years of medical training. Let’s repeat, that is 11-17 years of training. Let us emphasize what goes on in that training. When you look up differences, organizations ensconce the number of years, the accreditation, will play up that non-physician personnel saves money, they fill a need, they are just as good, let’s repeat, they are just as good. However, the difference lies in the training. In medical school, there is weeding so only the most strong-willed progress to residency. Hours and hours of studying occurs before becoming an M.D. or D.O. Students learn pathology, physiology, pharmacology, anatomy, surgery. These are subjects that are wide in breadth and intense which are difficult to even cram in 4 years. Then, there is residency. There is absolutely nothing on earth comparable to the extreme depth of residency training of physicians, absolutely nothing. Internship is spent learning generalities of a wide variety of general subjects. Residents are involved in codes, rotate in the ER, rotate in internal medicine, attend daily conferences, day in day out, day in day out, day in day out. Residency entails 90-hour weeks in some specialties and those who trained before 2002. Residents take detailed histories seeing patients, formulating a diagnosis, seeing patients in the ER, the ICU, and out-patient settings. Patients are presented every single day to a senior attending who have more breadth and knowledge as residents learn from their expertise. Nights are spent at work so that the progression of disease processes and management is understood. One makes split second life-changing decisions while gradually building responsibility. The craft is finely honed daily in the 3-6 years of residency training so that physicians are completely confident to enter practice or further training in fellowship, which is another 1-3 years. This will never ever be equivalent to any other type of training on earth regardless of the profession. This is what makes a physician a physician. That knowledge and skill set is irreplaceable unless the same training is undergone. Patients can tell a difference, physicians can tell a difference. It doesn’t matter how many other years other non-physician personnel may have trained or shadowed in the hospital, it will never be anywhere equivalent to the medical studies, residency, fellowship training, board examinations and most especially the vast wealth of experience that makes a physician a physician.

Patients entrust their health, their well-being and even their states of mind to their physicians. Physicians train not only for their specialties and subspecialties but they have the unique skill set to recognize subtle symptoms giving rise to other possibly devastating diseases. They are exposed to a myriad of diseases and are able to respond to chronic and to some of the most acute issues that encompass a vast fund of knowledge one can only derive from years of study and training. This can only come with the extensive training and experience which well-trained physicians have. When this perfect system and bond of a well-trained physician and a patient is broken, the system collapses. Physicians are terminated all over the country by administrators when they speak up about the diminishing quality of care when the less trained personnel deliver care or when denouncing profit over patient. Rather than addressing the problem at its roots, we place bandaids.

How did we come to this? A brief background of the demise of medicine

Once upon a time, private practices flourished. Physicians followed their own patients in the hospital setting. There were no teams. The relationship was between doctor and patient.

Recently, hospitalists cared for patients disrupting the continuity of care which has evolved into a team. All the patient knows is that many people in white coats were seen and the doctor’s name is not remembered. Fast forward to the future, solo private practices are as scarce as the dinosaurs that ruled the earth. Pressured by time-consuming requirements of health insurances, practices are increasingly sold to hospital corporations. Medical practices are disrupted and absorbed into larger healthcare systems. Patients are computerized files followed by everybody without a medical degree who are called doctors, practitioners and other misleading terms. This allows patients to believe they are still cared by medically qualified fully licensed physicians. Or even worse yet, we are now all called providers or healthcare providers to even the playing field of titles. Many different skill sets hide behind this title, a title coined by other sources so that everyone is deceptively equally skilled. Physicians should feel insulted when they are called provider. There are many campaigns that champion this course, advocating that it allows greater access to care and that rural places have no physicians. But the bottom line is the bottom line. It’s all about money and hiring the most economic labor for the most valuable skill set required. It has happened at the primary care level and anesthesiology level. They’ll soon be coming for the jobs of radiologists and surgeons if artificial intelligence and robotic technology do not intercede.

Health insurances and drug companies are the dominant forces having an illicit affair with each other, while we are the bystanders that are profoundly affected by their decisions. Physicians contract with insurance companies and render services to patients. Coding is the norm where a multitude of questions are answered and documented so physicians are reimbursed. This is why burnout is rampant and valuable face-to-face time is replaced. This works superbly for insurance companies. Businessmen rise in ranks dictating the quality of care.

Care is impeded by requirements of insurance companies. Physicians have to fight insurance companies in order to obtain an MRI of the brain for a patient they are worried might have a tumor. They undergo a process called a peer-to-peer review. A physician who is usually not a specialist employed by the insurance company reviews the clinician’s notes and determines whether the test will be covered. It might simple but not when it can take 15-20 minutes for one test. Multiply that by the number of tests that is reviewed. This is a wastage of valuable patient-physician time. This is a source of infinite frustration to physicians but insurances dictate the quality of care because they hold the purse strings for healthcare, controlling who gets the test. If it is denied then the physician and staff waste even more time appealing. If an MRI is ordered for a tumor, this may delay diagnosis and care where time is of the essence. Insurance companies obfuscate in hopes that tests or certain medications are not pursued, saving them money.

Patients who need specialists have to see their primary care doctor to get a referral in order to see a specialist which can delay care. Time is exceptionally important in cases such as in patients with oncologist conditions where every crucial day that is delayed in diagnosis may result in greater shortening of life expectancy.

Physicians are subconsciously dictated into referring within network because it is covered by health insurance even if a more qualified physician is a few feet away but may be out of the network. This boosts profitability within the insurance companies.

Appointments are reduced to 10 minute slots. Yes, they can be extended but physicians need to pay overhead, malpractice insurance, staff wages and any school debt. It is not financially feasible to see 8 patients in one day. Patients only see that their doctors are spending more time on the computer and have less eye contact. They feel unheard and unnoticed. They do not understand the pressures physician must face or that the system has transformed the quality of medicine. Physicians are at risk of an increasing number of errors because they work at a higher and higher levels. Those who supervise non-physician personnel oversee the care of up to 60 patients a day. These are worse conditions than residency because physicians assume all liability.

Where did things go very wrong?

One of the pivotal moments occurred when physician assistants and nurse practitioners assumed larger responsibilities, at times well beyond their training can handle. They are paid less than physicians and have trained substantially less than physicians yet work under the same conditions, giving medical advice, and writing prescriptions. They manage the care of a patient that was once the privilege of a physician. When I previously worked in New York City, I had the pleasure of working with some wonderful Physician Assistants and Nurse Practioners under neurosurgery. They called my neurological services when needed. They took care of the neurosurgical care of patients on the floor under the supervision of the neurosurgeon. But they knew their lane and worked under such. It was a well-oiled machine where everybody stayed in their lane. The quality of care was superb. Fast forward nearly over a decade, PA’s and NP’s manage complex patients on their own with a physician type role. The job description is completely different and the training is ill-fitting to such a role. This is where the problem lies.

Once upon a time, there were military corpsmen working side by side with surgeons during the Vietnam war. They checked blood pressures, started IV lines, recognized and triaged patients. They developed finely honed, valuable clinical skills. When the Vietnam war ended there were many medically skilled corpsmen whose skills would be wasted which how the position medical assistant was born. These jobs were created as a complementary position in aiding in healthcare. The positions of a PA and NP are similar, working as a complementary skill set in healthcare. They have a place in healthcare. But they were never originally intended to replace the extensive knowledge and skillset and training of a physician. To do so only invites a markedly different and not necessarily more superior quality of healthcare.

There are now nurse practitioners pushing for independent practice unsupervised to dole medical advice. They are a boon for any business administrator in medicine. In the hospital setting, one doctor could be supervising 5 nurse practitioners, therefore less financial burden on the part of hospitals. Liability is less expensive for hospitals because instead of 6 doctors they can pay for one while the doctor assumes more responsibility and all liability. The minute a physician speaks up about the quality of care they are dismissed quietly and either terminated or forced to resign. Many physicians do not come forward with their observations due to fear of retaliation or retribution. Many go on quietly working in other practices with the incident never to be spoken of again. They are gaslighted thinking they somehow did wrong by whistleblowing on the corruption of medicine. Very few come forward with their stories which they hide, feeling shamed and devastated.

How physicians and patients are fleeced alive

There are now many organizations working for physician recredentialing and maintenance of certification but the bottom line is profitability. Physicians supply the goods. Physician organizations work in cahoots with these other systems. While it is supposedly prestigious to be a member of a professional organization, everything is intertwined with money being the center. MOC (maintenance of certification) is a requirement entailing large fees in the hundreds annually and in the thousands over a decade. In Neurology, recertification and MOC over is a grand total of $23,580 over 30 years including examinations or $377,727,280 for more than 16,000 neurologists. This is highway robbery and doctors in every specialty are skinned alive. A physician cannot work in a hospital unless certified. A physician cannot be reimbursed by insurances unless you are certified. What was once voluntary is now coercion in order to drain from physicians. One of the very few non-corrupted professional pro-doctor organizations is the American Association of Physicians and Surgeons who are truly physician and patient advocates. The PPP or group for Physicians for Patient Protection is a pro-patient and pro-physician group that implements proactive work. Other grassroots physician-led actions are from members of the group Physicians Working Together.

Health insurances are misnomers. The health premiums run into the hundreds and thousands a month which do not kick in unless you completely paid off your deductible. A deductible is a deceptive term where one must shoulder thousands of dollars before the insurance coverage is activated. This is an incredibly profitable business for insurance companies because there is no return in investment until one is short several thousands of dollars. Healthcare is a universally needed commodity. Supply and demand dictates that the higher the necessity the more someone is willing to pay for that need, it’s sheer unadulterated business genius. Insurance companies work in close collaboration with pharmacies, drug companies which is why only certain drugs are approved. It steers that patient towards obtaining the drug with which the insurance company works with. There are other nuances about new medications, pharmaceutical drug company driven research data, connection of pharmacies, drugs and health insurances but that’s a whole different article that can be expounded at length.

It is 2018, medicine is now an extremely corrupted business of profit over patient.

One doctor decides to take a stand for patient care

However, one physician did decide to take a stand for patient care. http://padailypost.com/2018/03/20/medical-group-goes-doctor-1-4-million-legal-fees/ Diana Blum is a neurologist who worked in a medical practice in Palo Alto in 2009. When she became a shareholder and attended business meetings, she became more cognizant of the business dealings of the group. Some examples were reported to include not referring out of network, not using drug samples and other practices that increases profitability from a business aspect. When she commented on the negative impact on patient care she was labelled a “non-team-player,” “disruptor” and using “inappropriate comments.” She was reported as offered 3 options (1) resign to avoid negative letters of recommendation, (2) be terminated or (3) bring a claim or expose to the media knowing she might never work in that area again. She was reported as placed under PIP or performance improvement plan despite having some of the highest ratings in satisfaction by patients. She opted to resign under coercion. At one point, she consulted on one patient with reported negative impact from these types of practices and decided to take a stand. Many of the relevant facts were suppressed because the judge reportedly thought it might bias the jury. The judge was reported as siding with the other side as to who owes legal fees. There are still many details that Dr. Blum is not at the liberty of declaring since an appeal is ongoing. She reports there are many physicians in the same company with similar observations and pressures but cannot speak due to fear of retaliation and repercussions. This information was shared with her permission.

This marks the crossroads of medicine. After all the extensive documentation for electronic medical records, the shortening of the face-to-face time physicians have with their patients, the quiet rampant replacement of physicians with nurse practitioners and physician assistants where in some states they are allowed to work independently, this is one incident that must not be a small blip on the news, that must not be allowed to fade. It signifies a very important turning point in the standard of care.

It can easily be sensationalized or demonized but this sets the precedence of things to come. It signifies that a physician who advocates for patient care invites termination. If one brings claims against administration, the corporate office has an unending supply of legal arsenal to retaliate against that physician. This has to be one of the lowest points in medicine. This incident is of utmost importance because it sends a chilling message that essentially signals the suppression of physician voices all over the country. If physicians do not take a stand on behalf of patient care, who will? Physicians must be both physician and patient advocates. Nobody cares about physician burnout except physicians. It is of no consequence to anybody else if patients see less of their doctors except to physicians and patients. Both physicians and patients have been on the losing team these past few decades. We need to take back medicine or the only ones who will lose are the very ones it is supposed to serve.

How can we change the system?

Both physicians and patients need to be their own advocates. Patients must demand to see a physician, not non-medical doctor personnel and have a right to see their physician with whom they have the patient-doctor relationship. Other options are to look into direct primary care and take on catastrophic insurance. This bypasses the monthly costly fees to insurance companies. Physicians involved in direct primary care tend to have access to the lowest rates of medications and can direct patients to less costly outlets. Physicians in private practice and direct primary care have access and knowledge of companies with imaging studies with the most economic rates. Instead of a $3000 MRI deducted from the high deductibles paid out-of-pocket, a wholesale type price straight from the company can be $300. Patients need to be their own advocates by taking care of their health. Everything is interconnected, including the fast food industry, the companies that manufacture processed food, the drug companies, the insurance companies, and the health industry. Everything is big business. When people are chronically ill related to a lifestyle of unhealthy food they need medicine, they need healthcare. It’s an unending profit cycle. Each business feeds into each business. It’s a merry-go-round of profits. Healthy people do not need to see physicians. Prevention is key to keeping the doctor away. Fewer patients mean less shortage which means better quality care from physicians.

Physicians do not need to hang their heads low accepting the workload they are given. There are other options including direct primary care, entering private practice, and deleting insurance companies. Speaking up and raising awareness of these issues should not be discounted. Many physicians are resigned to the fate of medicine but it does not have to be that way. There are physician activists who are well adept and fighting the worthy cause through legislation, including Dr. Westby Fisher who is working to fight MOC. This includes a recent success story of Dr. Craig Wax winning the battle along with 3 other doctors untying professional membership from board certification. There are physician advocates raising awareness of the exorbitant pricing of medications and kickbacks such as that seen in the work of Dr. Marion Mass. Officials have taken note. Physician writers who are well-connected can raise awareness of these current conditions. If you see something say something. Physicians should demand they be called Doctor and Physician not provider, not health care professional, not health care provider. It is an insult to your nearly 11-17 years of training to be called anything other than that. We are physicians who studied to take care of patients to the best of our ability. It is because of our very complacency and the burgeoning work requirements which have caused these current issues. Nobody else will extricate physicians and patients from these predicaments except ourselves. One day everybody will be a patient, if healthcare is worrisome now, its deterioration will only continue to worsen. The next generation will not even understand what excellent healthcare is because they would have never experienced it which is very sad.

It is easy to be complacent but one day every single one of us will be affected whether at work or at the doctor’s office. When someone’s mother with a devastating disease is cared for by a physician assistant who knows nothing about that patient and has to step outside 4 times to check on records and cannot answer the most important questions, one knows it is time to make a change for the better. It is troubling to say the least when you see a medical office plaque for subspecialty with 16 doctors in white coats caring for the sickest group, when on closer inspection 8 of them are nurse practitioners and physician assistants. In a few years time, there will be fewer with M.D.’s and D.O.’s after their names. One day there will be one licensed physician handling a whole department on non-physician staff.

As I leave my business cards with doctors offices, I am shocked to discover that some practices have non-physicians who are 1/2 the staff on their shingle, especially hospital practices. One day it will be one doctor and the rest non-physicians. Is this really the way we want medicine to become? Physicians are leaving medicine by the droves and are fed up with the state. Others feel powerless and feel that this is their only recourse bogged down by huge loans and personal responsibilities.

Call to action

Medicine has essentially become a business, an industry, profiting from physicians and patients, employing the least trained personnel to replace and step into their shoes and depriving patients of quality time and care they deserve. In a few years, medicine will become a shell of what it used to be, it will only deteriorate further if nothing is done now. In watching idly continuing about with our business, we are complicit with its decline. If a physician such as Dr. Blum cannot even fight the good fight for patient care and cannot reason that the ongoing healthcare policies are detrimental only to be suppressed and devastated for speaking up, then the rest of us are doomed.

One of the basic tenets of serving as a physician is “primum non nocere,” first, do no harm. To stay silent on these issues grossly impacts patients in a negative manner. But how do we advocate for patients when we are silenced and censored? Dr. Blum is devastated and suppressed for advocating for good patient care. She is the sacrificial lamb in standing up for care. It strikes a chord in many physicians because this is why we chose this profession and trained hard for it. We cannot let medicine be ruined. We rise above it. If we can soldier through 90-hour work weeks during intense training which no sane person would want to experience, why should we let non-physician administrators dictate how we practice or decide that we make inappropriate comments. It is every bit of convolution. If a stand is not taken now when will this descent end?

Medicine is in shambles today because we are complicit and enabled this to happen, perhaps not by choice but by inaction. All the wellness programs in the world will not reverse the underlying cause of the dilemma. The quandary is that healthcare is reduced to a masterful game of production and profit, the pawns are patients and physicians.

We must actively take ownership of our responsibility to our patients, pick up the shards and rebuild the patient-centered system it is supposed to be. We can do this, every single one of us by not tolerating these conditions by saying no to the current state of affairs. Some details have been outlined. By not enabling the way medicine is practiced we can make a change. By giving our patients the best of ourselves and not just snippets of time resulting in a gross overload of work we are not doing a justice towards our responsibility towards our patients or ourselves.

Discussing it does not work. But if every single one of us changes our work habits maybe even our work by doing DPC or something similar we take back medicine so we practice how it is supposed to be and not under the restrictive conditions of a profit-driven insurance company. When you’ve practiced under both conditions you see a huge difference. The horse is already out of the barn. But who else will care enough to fix this mess and make changes, nobody else but us.

Primum non nocere, first, do no harm. This is our calling, this is our truth.

Virginia Thornley, M.D. is a neurologist who writes at https://neurologybuzz.com/



Sunday, 16 September 2018

The Return Of Capsaicin Patches For Nerve Pain

Today's short post from clinicalpainadvisor.com (see link below) retuns to capsaicin patches as being efficient pain relievers, especially when it comes to neuropathic pain. The problem was and still remains, the discomfort that high-strength capsaicin patches can bring if not applied properly and then monitored thereafter. As you probably know, capsaicin is the component of chili peppers that makes them hot. This article refers to a recent small-scale study that has concluded that the patches can be extremely efficient in reducing nerve pain but reduces the potential side effects to 'mild pain at the application site'. This could be misleading for many people, who have been shocked by the pain these patches can bring and must be one of the main reasons that they really haven't caught on as much as some companies hoped. It's strongly advised that if you consider using these patches, that you apply them with medical supervision and that you ask your doctor to monitor the effects over a period of time. The burning problems they can cause should not be underestimated!

Capsaicin 8% Patch Effective, Safe for Localized Peripheral Neuropathic Pain
Clinical Pain Advisor Contributing Writer September 14, 2018

  Study participants were given a capsaicin 8% patch to be applied to the upper and lower extremities for the treatment of postherpetic neuralgia, postoperative cicatrized pain, or other localized perip

The following article is part of conference coverage from the IASP 2018 conference in Boston, Massachusetts. Clinical Pain Advisor's staff will be reporting breaking news associated with research conducted by leading experts in pain medicine. Check back for the latest news from IASP 2018.

Capsaicin 8% patch has demonstrated efficacy and safety in improving pain, allodynia, and hyperalgesia associated with a wide range of localized peripheral neuropathy types, according to a study to be presented at the 2018 World Congress on Pain, held September 12-16 in Boston, Massachusetts.

This multicenter observational study included 60 participants (60% women; mean age, 50.9 years) who were given a capsaicin 8% patch to be applied to the upper and lower extremities for the treatment of postherpetic neuralgia (n=8), postoperative cicatrized pain (n=24), or other localized peripheral neuropathic pain (n=26). The capsaicin patch was used in combination with regular analgesic treatments for localized peripheral neuropathic pain. Average continuous daily pain was assessed with a 0 to 10 visual analog scale.

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Reductions were observed from baseline to the end of treatment in continuous daily pain (from 6.8 to 4.1, respectively), mechanical allodynia (from 7.9 to 4.2, respectively), and hyperalgesia (from 7.4 to 4.4, respectively). Physical functioning improved from baseline in 31 patients (49%), and 39 study participants (65%) reported experiencing analgesia after the initial application. The patch was re-administered after a mean of 87 days in this cohort.

The most reported adverse events related to treatment was mild pain at the application site, with 43 participants reporting erythema, 27 participants reporting a sensation of burning, and 13 participants experiencing pruritus. The majority of patients (80%) reported adequate to good satisfaction, the remaining reporting poor satisfaction with the patch.

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Capsaicin Patch Superior to Pregabalin for Alleviating, Resolving Dynamic Mechanical Allodynia

The study researchers conclude that “Repeated treatment [with the capsaicin 8% patch] improved continuous pain relief, hyperalgesia and allodynia in a broad range of localized peripheral neuropathic pain etiologies. Capsaicin 8% patch was well tolerated…[and] is a suitable treatment option for localized peripheral neuropathic pain in monotherapy or combined with other analgesics.”

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Galvez R, Maldonado J, Vela A, et al. Repeated treatment with capsaicin 8% patch in localized peripheral neuropathic pain.Presented at the World Congress on Pain 2018; September 12-16, 2018; Boston, MA. Poster 64478.


Saturday, 15 September 2018

How Useful Could Immunoglobulin Therapy Be For Nerve Damage Patients?

Today's truly fascinating post from healthrising.org/blog (see link below) offers something new (for a change) that may prove to be revolutionary for people living with neuropathy and other autoimmune diseases. It talks about IVIG treatment
(Intravenous immunoglobulin) and the struggles to implement large scale studies against the wishes of health insurance companies who refuse to pay for it. Nevertheless, IVIG (Immunoglobulin therapy) could be a very effective treatment for many neuropathy patients. So what is IVIG? WebMD sums it up by saying "Your body's immune system normally makes enough antibodies to fight germs that cause infections. But if you have an immune deficiency, your body can't make enough of them. ... IVIg gives you antibodies that your body is not making on its own so you can fight infections." It's primarily used to treat people with poorly functioning immune systems but reading the article, you will quickly realise the implications for people with a compromised nervous system. Absolutely worth a read but don't get your hopes up that it will soon come to a doctor's prescription pad near you - insurance companies will fight tooth and nail to prevent such an expensive treatment being covered by health insurance.

The Case for IVIG Treatment in Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, Small Fiber Neuropathy, and POTS : IVIG#3
by Cort Johnson | Sep 13, 2018 |

Cortene To Trial New Drug for ME/CFS

“The bottom line is that we should rethink this whole area and encourage proper clinical trials.” Dr. Nancy Klimas

This article is the last of a three-part series on IVIG which came out of my attending the 2018 Dysautonomia Conference in Nashville, Tennessee.

An IVIG Chronic Fatigue Syndrome (ME/CFS) / POTS Treatment Success Story: IVIG#1
Are Chronic Fatigue Syndrome, POTS and Fibromyalgia Autoimmune Dysautonomias? IVIG #2
The Case for IVIG Treatment in Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, Small Fiber Neuropathy, and POTS: IVIG#3

What evidence exists for the use of IVIG in ME/CFS, FM and POTS?

IVIG is a very expensive but commonly prescribed immune modulating drug used extensively in autoimmunity and immune deficiency. The article examines the evidence base for IVIG in chronic fatigue syndrome (ME/CFS), fibromyalgia and POTS and looks to the future to see what possibilities may emerge.

I queried ME/CFS experts on their use of IVIG in ME/CFS/FM and did a literature search. Four experts answered – Dr. Lapp, Dr. Sivieri, Dr. Klimas and Dr. Levine. Dr. Lapp and Dr. Sivieri sent short replies and Dr. Klimas and Dr. Levine – both obviously very interested in this drug – sent several page-long answers. Dr. Klimas, an immunologist, provided both a historical and present-day overview of the drug’s use in ME/CFS.

About IVIG (Intravenous Immunoglobulin) Treatment

Available since the 1950s, IVIG contains massive amounts of gamma globulins or antibodies which are gathered from the plasma of at least a thousand healthy donors. (Dr. Schofield noted in her video, though, that it probably comes from many thousands more.) Filtering the plasma to get the antibodies and produce the IVIG takes upwards of nine months.

Dr. Klimas believes that the pooling of IVIG from a large population gives it a “tremendous advantage”. If an infection is the problem, then potential protection provided by the product is so complete that you don’t necessarily need to know what virus is present – you just need to boost your immune functioning with the product.

IVIG is a blood product used to fight off infection, boost immune system functioning or tamp down inflammation in people with inflammatory, autoimmune or neurological diseases like Guillain-Barre syndrome, lupus, multiple sclerosis and others. People with immunoglobulin deficiency states (low levels of immunoglobulins or immunoglobulin subclasses) who experience recurrent infections are eligible for IVIG.

First used to boost the immune systems of people with immune deficiency disorders, IVIG is now mostly used as an anti-inflammatory treatment to combat autoimmune disorders. It’s been used in virtually every autoimmune disorder. Dr. Klimas reported that the list of diseases treated with IVIG grows longer every year. IVIG has an advantage over some of the monoclonal treatments used in autoimmune diseases because it’s safer and not as immunosuppressive.

It’s also used as a treatment of last resort in a number of disorders.

Three Types of Gamma Globulin Products

Gamma globulins can be administered in three different ways – via infusion (IVIG), subcutaneously, and intramuscularly.

Intravenous gamma globulin (IVIG) – The most commonly used form of gamma globulin is administered intravenously, usually once a month but sometimes weekly. If it’s administered monthly, IgG levels will rise and then dip, leaving a gap in coverage during the month.

Subcutaneous gamma globulin – One advantage of the subcutaneous product is its ability to be self-administered. Dr. Lapp pointed out that you can even throw it into your suitcase and travel. The fact that it produces steady levels of immunoglobulin makes it probably more effective in people who are fighting off infections. Dr. Levine reported that she’s switching some of her patients to weekly subcutaneous injections of Hyzentra in order to achieve more even levels of gamma globulin in their bloodstream.

The subcutaneous form has mostly been used to restore immunity and fight off infections, but Dr. Klimas reports that for people with autoimmune diseases a single high dose IV infusion followed by weekly, lower dose subcutaneous injections can be effective as well.

Intramuscular gamma globulin – is not commonly used. In the first 10 years of her career (80s and early 90s), though, Dr. Klimas reported that she used a lot of IM gamma globulin and her clinical impression was that it was very helpful. During the Gulf War (1991), however, the army bought all of the available IM gamma globulin and it was off the market for several years. When it came back on the market it was prohibitively expensive.

Now, even though intramuscular GG is less expensive than intravenous gamma globulin, she’s rarely able to get it. She finds it easier to get IVIG or the equally expensive subcutaneous product.


IVIG is produced by a number of companies that make different brands of IVIG. Because the IVIG brands can differ in so many areas (concentrations, formulation, osmolality, product stabilizers, sodium concentration, anti-infective activity, IgA content and pH) it can, at times, be important to match the patient to the right brand of IVIG.

Dr. Levine prefers Gammagard. Dr. Klimas reported that the insurance company usually decides the brand and her experience is that the results are generally similar across brands.

Dosing Regimens and Safety

IVIG is usually given every couple of weeks, often needs to be given continuously (not a cure) and is incredibly expensive (can cost $100K a year). The risk of aseptic meningitis is low but increased in patients with autoimmune dysautonomia. That problem can be ameliorated by slower infusions and hydration. Blood clots and kidney toxicity are two other rare complications.

Two dosing regimens exist: a low dose one for patients with low antibody levels (immune deficiencies) and a higher dose for patients with autoimmune dysautonomia who need the extra antibodies in the high-dose IVIG to swamp the bad ones producing their disease.

Schofield usually starts out with 1 gram/per kg in her autoimmune patients, and that’s usually enough, but she can go up to two g/kg monthly.

Schofield warned that giving IVIG slowly and using aggressive hydration is important in her POTS patients. She generally starts off with 1/4 g/kg weekly and works up to 1 g/kg given all at once. (Some patients peak at ½ g per kg. She warned never to give IVIG and fluids at the same time.)

Schofield and Dr. Klimas agreed that in ME/CFS (where IgG1 and IgG3 – which fight off viruses – are more important), weekly injections are more likely needed to ensure constant antiviral protection in some patients because the half-lives of these antibodies are shorter.

Why IVIG Works When it Does

IVIG provides antibodies that can boost and rebalance the immune response.

Many different hypotheses have attempted to explain IVIG’s success. One idea is that it stops autoantibodies from binding to their targets. Another is that it binds to and halts autoreactive B-cells that produce dangerous autoantibodies. Yet another is that it hastens the degradation of pathogenic antibodies or that it scavenges complement (C3b, C4b) proteins before they can cause tissue damage. All these hypotheses may, in fact, be accurate in different diseases.

IVIG in Chronic Fatigue Syndrome (ME/CFS)


Significant interest in gamma globulin resulted in several clinical trials in the 1990s that had mixed results. Peterson’s 33-person placebo-controlled blinded 1990 study found widespread evidence of immunoglobulin deficiencies. Despite restoring some of the deficiencies, the six-month trial of IVIG given monthly found no evidence of significant improvement.

Hickie et. al. found improved mood and immune functioning in a smaller 1992 IVIG trial and Lloyd’s placebo-controlled 1990 trial found significant improvement in approximately 40% of patients with many resuming work and other activities. Lloyd’s larger 99-person 1997 follow-up trial, however, was unsuccessful, as was a smaller American trial that targeted IgG deficient individuals. The Lloyd study, the largest ever done in ME/CFS, found high levels of side effects and reported that “Intravenous immunoglobulin cannot be recommended as a therapy for the treatment of CFS. A better understanding of the pathophysiology of this disorder is needed before effective treatment can be developed.”

Dr. Klimas, however, pointed out two glaring problems with the study. First, it included autoimmune (high dosing) patients and it used a subpar product whose impurities eventually forced it from the market. If the dosing had been lower and a different product had been used, the outcome might have been different. Plus, the trial only lasted for three months.

Dr. Klimas believes that Stephen Straus’s 1997 editorial, “Intravenous Immunoglobulin Treatment for the Chronic Fatigue Syndrome”, published in the American Journal of Medicine, effectively put an end to IVIG clinical trials in ME/CFS.

Rowe’s 1997 IVIG trial, on the other hand, found significant functional improvement as did her five year follow-up. Rowe’s five year follow-up was reported in a publication (Journal for Chronic Fatigue Syndrome) that was unfortunately not included in medical indexes such as PubMed and therefore was not widely disseminated.

In 2003, Jonathan Kerr reported that IVIG treatment in three cases of parvovirus associated ME/CFS led to a resolution of symptoms, improved functional ability and normalized cytokine tests. A 2005 case report of a young boy with parvovirus associated ME/CFS treated with IVIG had the same result. A 2015 case report of an ME/CFS patient with documented parvovirus infection, however, found IVIG had a paradoxical effect, increasing viral replication and symptoms.

Autoimmunity, Inflammation and ME/CFS

Dr. Levine reported that the finding of antibodies against the receptors on blood vessels in a subgroup of ME/CFS patients may open the door for these patients to be treated for ”autoimmune autonomic gangliopathy”. Studies are underway at several centers to assess IVIG’s effectiveness in these patients. If the results are positive, that should open the door for the use of IVIG in ME/CFS patients with high levels of these antibodies. The German CellTrends lab is the only lab doing these tests at the moment.

Dr. Levine reported that another possiblly helpful diagnosis for obtaining access to IVIG treatment is ”inflammatory neuropathy” (burning, pain, tingling in the extremities and sometimes loss of reflexes and/or abnormal EMG response) which has been validated by a neurologist. (The dosing schedule for inflammatory neuropathy is a bit higher and more frequent (1-2 gms/kg for a 50 kg woman or 50 to 100 gms daily for two days in a row every 2-3 weeks for a total of five or six doses.)

Dr. Klimas believes gamma globulin could offer a two-for-one option for one set of patients: ME/CFS patients with an immune deficiency and viral reactivation but who also have an autoimmune condition.

See below for autoimmune diagnoses which may in the future assist some people with ME/CFS get IVIG.


IVIG appears to be like many other drugs/treatments for ME/CFS. Some people – probably a small percentage – do really well, more do moderately well, and some do not respond at all. Dr. Sivieri has reported before that IVIG can be effective but believes it works best when administered within a total treatment paradigm.

In Dr. Levine’s experience, gamma globulin given either intravenously or subcutaneously is a moderately effective treatment in ME/CFS patients who frequently suffer from upper respiratory infections or who experience chronic flu-like symptoms. If infections are a problem, sometimes she’ll reduce the infusion frequency (to every 6 weeks) during the summer months.

IVIG’s effectiveness should increase as the autoimmune subsets in ME/CFS/FM and POTS become better elucidated and more easily targeted.

Getting Coverage

All the experts agreed that insurance companies want to see evidence of an immune deficiency and active infections. Dr. Lapp reported he only had a low number of patients on the products because insurance companies will “fight harder than a marlin on a hook” to keep from paying. Similarly, Dr. Sivieri wrote that while he is still “doing a fair amount” of IVIG, it is, in his experience, getting harder and harder to get insurance companies to cover it. If the trend continues, he worries about IVIG becoming a “lost” treatment.

Dr. Levine reports that insurance companies most commonly want test results showing that a person’s immune system does not get boosted by a vaccine shot. If the immune boost is not seen, the patient is diagnosed as having Common Variable Immunodeficiency (CVID) and can be eligible to receive monthly IVIG infusions.

Even though “dead” vaccines seem less problematic than live vaccines in ME/CFS, administering any kind of vaccine to an ME/CFS patient can be problematic. Since insurance companies have decided that the vaccine test is the gold standard for coverage, getting it via other routes is more difficult.

Lacking the vaccine challenge, Dr. Levine’s experience is that at least four annual episodes of sinusitis, bronchitis or other infections requiring the use of antibiotics are needed to get covered. (A bout of sinusitis can send some people into a relapse and IVIG can stop that.) She noted that insurance companies will sometimes even request receipts for antibiotics from the pharmacy to show that the patient has filled these prescriptions.

Finding evidence of autoimmunity (autoimmune polyneuropathy, autoimmune autonomic gangliopathy) is another option which may emerge in the next couple of years.

If you have ME/CFS or fibromyalgia, keep reading! The next sections may apply to you.

IVIG in Small Fiber Neuropathy (Polyneuropathy)

These families’ relentless testing for treatable causes of their children’s chronic pain generated the abundant data analyzed here. Oaklander and Klein

Dr. Oaklander reported some promising results using IVIG in children with a putative diagnosis of small-fiber polyneuropathy (SFPN); e.g. small fiber neuropathy (SFN). SFPN or SFN has been documented in fibromyalgia and is being documented in chronic fatigue syndrome (ME/CFS). (Both Dr. Systrom and Dr. Kaufman have found it extensively in ME/CFS; Systrom will presumably report on this soon in a study.)

Findings of a small fiber neuropathy can help one’s chances of getting IVIG.

This was an ME/CFS/FM/POTS/EDS type group for sure. The most common “label” attached to these patients was fibromyalgia. Others included most of the long list of diseases or conditions associated with this illness complex: “functional disorder”, central sensitization, chronic fatigue syndrome (ME/CFS), POTS, irritable bowel syndrome, migraine, chronic headache, EDS, myofascial pain syndrome and chronic (treatment resistant) Lyme disease. Almost 70% of the participants were disabled. Sixty-one percent attributed the onset of their illness to an instigating infection or injury.

IVIG was tried in eight patients who didn’t respond to corticosteroids or who required long-duration treatment. Three did not respond but five received significant improvements including, in those who were tested, improvement on autonomic tests (Tilt, Valsalva, heart rate variability).

Autoimmune SFPN (AaSFPN)

Now calling the condition “autoimmune SFPN (aaSFPN)” Oaklander’s larger IVIG study (n=55) found 74% of the participants rating themselves ‘improved’ and their neurologists calling 77% of them IVIG responders. Almost 40% reported that they were “very much improved”. Ten percent reported they were worse. For some reason, males responded spectacularly with 100% improvement rates while females had 61% improvement rates.

Sixteen percent of the participants entered a sustained long remission (average of 20 months). The study, interestingly, tried the highest suggested dose first (1.3–2.0 g/kg/4 weeks) and then titrated downwards, if necessary. It also lasted longer than many trials (at least 3 months).

Only one-quarter of the participants had a “systemic” autoimmune diagnosis (high ANA titers) while three quarters had a small fiber autoimmunity that was restricted to the small nerve fibers in the body (and wouldn’t be picked up by standard blood tests).

Except for transient infusion reactions (headaches, nausea, flu-like symptoms, stiff neck) which were common (60%) and addressed by slowing infusion rates, hydrating patients, etc., side effects were low.

The authors asserted that their results “imply that aaSFPN may be far more common than appreciated” and “provide strong evidence that medical insurers should no longer reflexively decline to pay for IVIG treatment of aaSFPN.”

The data is clearly calling out for a large placebo-controlled trial in SFPN. Given the rigorous classification of the patients, a successful larger trial could open the door for treatment of a significant subset of ME/CFS/FM patients with documented SFPN.


Back in 2008, Carol found that a third of fibromyalgia patients had a chronic demyelinating polyneuropathy. He reported that a brief IVIG treatment significantly improved pain, tenderness and strength.

Postural Orthostatic Tachycardia Syndrome (POTS)

No studies have examined IVIG’s effectiveness in POTS, but Goodman reported good results at the 2018 Dysautonomia conference and recently published a case report in which IVIG, low dose naltrexone and antibiotics (for SIBO) resolved the POTS of a severely ill patient.

In 2018, Dysautonomia International funded the first placebo-controlled pilot IVIG trial ever in POTS. (The trial is already filled but if it succeeds a larger trial will open up.)


The case for the use of IVIG in treating ME/CFS/FM/POTS in the medical literature has mostly consisted of small clinical trials and case reports. The findings are mixed with more recent, better targeted studies being more positive, but the studies are too small and lack the rigorous placebo controls needed to get doctors to prescribe it or insurance companies to cover it. Larger studies are underway, however.

Suzi’s successful IVIG story demonstratives how effective the drug can be in the right ME/CFS/POTS patient. The real excitement with IVIG lies in the future with the validation of autoimmune subsets which affect the small nerve fibers the blood vessels or possibly the mitochondria in ME/CFS, FM and POTS. The emergence of those subsets will likely result in the reconfiguration of the ME/CFS/FM/POTS disease group. Successful IVIG trials in autoimmune POTS and small fiber neuropathy, if they occur, should open the door for more insurance coverage of this expensive drug in these groups.

IVIG Series
An IVIG Chronic Fatigue Syndrome (ME/CFS) / POTS Treatment Success Story: IVIG#1
Are Chronic Fatigue Syndrome, POTS and Fibromyalgia Autoimmune Dysautonomias? IVIG #2
The Case for IVIG Treatment in Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, Small Fiber Neuropathy, and POTS: IVIG#3

Other Articles from the Dysautonomia Conference
2018 Dysautonomia International Conference I: Small Fiber Neuropathy, POTS, MCAS and Vagus Nerve Stimulation
The 2018 Dysautonomia Conference Pt. II: Could You Have a Spinal Fluid Leak? An ME/CFS, POTS, FM Perspective
Dysautonomia International Conference Pt III: The Autoimmunity Revolution in POTS
“Sticky Blood” – Antiphospholipid Syndrome, POTS, Chronic Fatigue Syndrome and Fibromyalgia – The Dysautonomia Conference #4
Stagnant Hypoxia – Where Chronic Fatigue Syndrome and Hyperadrenergic POTS Meet?
Promise Fulfilled – A New Chronic Fatigue Syndrome / Fibromyalgia Practitioner Steps Fort


Friday, 14 September 2018

Aquatic Exercise: The Most Comfortable Form Of Exercise For Neuropathy Patients (Vid)

Today's YouTube video from the Neuropathy Alliance of Texas (see link below), is more than a half hour long, has the visual quality of pea soup and with the greatest respect for the speaker, is one of the most boring presentations you'll see in a long time. That said...the content is extremely useful for neuropathy patients who have difficulty with pain-free walking, balance issues and weakening joints and muscles. It talks about using aquatic exercises to improve both your physical condition and the relief of the symptoms that can make any sort of strenuous exercise out of the question for many patients. Despite the fact that the video is not the most media-sexy you'll ever see, it really is worth sitting through and maybe applying to your own situation. The weightless aspect of aquatic exercise makes it one of the most attractive for nerve damage sufferers - the pain involved with the exercises is so much less than working 'on dry land', so maybe it's worth investigating for you - however reluctant you may be and however negative your exercise experiences have been in the past.

Aquatic Exercise for Neuropathy 

- Julie O'Connor, BS, AEA Neuropathy Alliance of Texas Published on 1 Apr 2016


Thursday, 13 September 2018

Did You Know That Vitamin Deficiency, Toxins And Medications Can Cause Neuropathy?

Today's extensive post from ncbi.nlm.nih.gov (see link below) tells you all you need to know about how vitamin deficiencies, toxins and medications can actually be the cause of your neuropathy themselves, without any other medical condition being involved. Despite the massive amount of useful information, perhaps the most useful lesson to be gained from reading this is that you should definitely not rush down to your supplement store and start swallowing vast amounts of what you may think you're deficient in. You need to talk to your doctor, neurologist, dietician etc etc and get their advice first. You also need to find out which of these deficiencies and toxins may apply to you and that can often be done by means of testing. After that, doing your own research on individual points from the article will help you understand them much better and be able to make a more measured decision as to where to go from there. The article is not an easy read and is full of technical terms but it's still very informative and may alert you to things you may not have considered when looking at the reasons for and ways to help your particular neuropathy. It's also an article that may cause a bit of panic in your mind but remember, all the things mentioned here are just possibilities and not certainties. If you need professional advice, ask for it before taking steps to address things yourself.

Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications
Nathan P. Staff, MD, PhD and Anthony J. Windebank, MD, FAAN
Author information ► Copyright and License information ► Disclaimer
This article has been cited by other articles in PMC.

Continuum (Minneap Minn). 2014 Oct; 20(5 Peripheral Nervous System Disorders): 1293–1306.
doi: 10.1212/01.CON.0000455880.06675.5a
PMCID: PMC4208100
PMID: 25299283

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Purpose of Review:

Peripheral neuropathies secondary to vitamin deficiencies, medications, or toxins are frequently considered but can be difficult to definitively diagnose. Accurate diagnosis is important since these conditions are often treatable and preventable. This article reviews the key features of different types of neuropathies caused by these etiologies and provides a comprehensive list of specific agents that must be kept in mind.
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Recent Findings:

While most agents that cause peripheral neuropathy have been known for years, newly developed medications that cause peripheral neuropathy are discussed.
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Peripheral nerves are susceptible to damage by a wide array of toxins, medications, and vitamin deficiencies. It is important to consider these etiologies when approaching patients with a variety of neuropathic presentations; additionally, etiologic clues may be provided by other systemic symptoms. While length-dependent sensorimotor axonal peripheral neuropathy is the most common presentation, several examples present in a subacute severe fashion, mimicking Guillain-Barré syndrome.
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Toxins, medication side effects, and vitamin deficiencies frequently damage the peripheral nervous system. This susceptibility is likely a result of the metabolic demands of a neuron whose cell body and distal axon can be several feet apart. While the peripheral nervous system may be the primary organ system affected in these conditions, peripheral neuropathy often occurs within a multisystem constellation of dysfunction (Table 7-1). Knowledge of the syndromic presentations can facilitate prompt, accurate diagnosis and subsequent treatments.

Table 7-1

Other Systems Involvement That May Provide Clues to Etiology of a Peripheral Neuropathy Due to Toxicity or Vitamin Deficiency

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As with most types of peripheral neuropathies, acquiring a detailed history is crucial to the diagnosis of neuropathies caused by toxic agents and vitamin deficiencies. Careful attention must be paid to occupational and home exposures. In particular, asking about recent changes in exposures may provide useful information, as many of the toxic exposures result from new day-to-day habits. While most forms of malnutrition no longer plague developed societies, a history of gastric surgery, chronic malabsorption, or alcoholism may predict the presence of vitamin deficiencies. It is important to take a complete review of systems to determine whether a multisystem syndrome is present as this may lead to a correct diagnosis.

It is also important to recognize that other causes of neuropathy may mimic what is suspected to arise from a toxic source or a vitamin deficiency. For example, a patient with more sensory loss on examination than expected from considering his or her history, combined with high arches and hammertoes, may reflect a long-standing hereditary neuropathy that has finally become symptomatic (especially in the setting of a positive family history of neuropathy). Most toxic and vitamin deficiency–related neuropathies present in a length-dependent fashion with axonal pathology (apart from some notable exceptions detailed below). Therefore, in a neuropathy with significant asymmetry, polyradicular, or mononeuritis multiplex presentation, other etiologies should be explored further, even in the setting of documented toxicity or vitamin deficiency.
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Vitamin B12

Causes of vitamin B12 deficiency can be organized by where the absorption defect occurs. A diet containing minimal animal products provides sufficient vitamin B12, so severe deficiency due to poor intake occurs only in the case of strict veganism. Within the stomach there are several etiologies that degrade the ability of vitamin B12 to bind with intrinsic factor, including pernicious anemia, atrophic gastritis, prolonged antacid use (proton-pump inhibitor or H2-antagonists),1 and gastric bypass. The final absorption of vitamin B12 in the terminal ileum may be interrupted by Crohn disease or surgical resection.2 The main pathology of vitamin B12 deficiency is subacute combined degeneration within the spinal cord with loss of both corticospinal tracts and posterior columns with a concomitant axonal sensorimotor peripheral neuropathy. It is important to note that because of the involvement of the cervical spinal cord early in disease, sensory symptoms in both hands and feet may present simultaneously and provide a clue to etiology.3

On examination, the patient will exhibit signs of both upper and lower motor neuron dysfunction (sometimes appearing as decreased reflexes with a Babinski sign). Vitamin B12 deficiency is also associated with cognitive dysfunction. Megaloblastic anemia may be present as well, owing to the importance of vitamin B12 in DNA synthesis.

Testing to confirm vitamin B12 deficiency should include both serum vitamin B12 and methylmalonic acid, which is a more accurate marker of cellular vitamin B12 levels and may be abnormal in the setting of low-normal vitamin B12 levels. Elevated levels of gastrin and intrinsic factor antibodies can also establish the diagnosis of pernicious anemia. Supplementation for vitamin B12 deficiency should be provided parenterally since poor oral absorption is usually the cause of the disease. Supplementation with vitamin B12 typically halts progression of the disease, but does not reverse it since much of the disability is secondary to the spinal cord pathology. Supplementation recommendations for vitamin B12 and other vitamin deficiencies are outlined in Table 7-2.

Table 7-2

Vitamin Supplementation Recommendations in Symptomatic Vitamin Deficiencies


Acquired copper deficiency may look very clinically similar to vitamin B12 deficiency and should be investigated in parallel with patients presenting with a myeloneuropathy.4 Copper is absorbed in the stomach and small bowel, and gastric surgery has been associated with copper deficiency. Additionally, copper absorption is competitive with zinc absorption and reports have shown an association between use of zinc supplementation and presence of copper deficiency (Case 7-1). Therefore, it is useful to test both copper and zinc when this condition is suspected. Anemia is also a common complication of copper deficiency.

The treatment strategy for copper deficiency is to combine copper supplementation with identifying and removing excess zinc intake.5 The goal is to halt progression of the myeloneuropathy as reversibility may be limited.

Case 7-1

A 65-year-old man with no significant past medical history developed progressive gait ataxia over a 3-month period. He had multiple falls without significant injuries. He progressed to requiring a walker for gait stability at the time of his examination. He denied any frank weakness, bowel/bladder difficulties, erectile dysfunction, orthostatism, dry eyes/dry mouth, or cognitive changes. There was no family history of neuromuscular diseases.

On neurologic examination, the patient had normal mentation and cranial nerves. He exhibited mild weakness in toe extensors, but strength was otherwise intact. Tone was normal and no tremor was present. He had decreased sensory perception to light touch, vibration, and joint position sense up to the ankles, and heat-pain sensation was normal. Reflexes were brisk at the knees and reduced at the ankles, and Babinski sign was present bilaterally. There were no abnormalities on finger-to-nose or heel-to-shin testing when allowing visual cues. He exhibited a wide-based gait, but was able to rise on his toes and heels. He was unable to tandem walk and had a positive Romberg sign.

MRI of the cervical spine demonstrated nonenhancing, mild T2 hyperintensity of the dorsal columns from C3 to C6 without any spinal canal stenosis. Nerve conduction study showed reduced amplitudes of lower extremity compound muscle action potentials and absent sural sensory nerve action potentials. Conduction velocities, distal latencies, and F waves were normal. On EMG, long-duration motor unit potentials were observed in distal musculature. The study was interpreted as consistent with an axonal sensorimotor peripheral neuropathy.

Laboratory studies were notable for a microcytic anemia, reduced serum copper level, and increased serum zinc level.

On further review of systems, the patient endorsed taking megadoses of zinc supplementation, and was treated with oral supplementation of 2 mg elemental copper daily. His symptoms stabilized, and he noted some functional improvement after intensive physical therapy.

Comment. This case illustrates a copper deficiency myeloneuropathy, which presents in a similar fashion to subacute combined degeneration and may be associated with excessive exogenous zinc supplementation (either through supplements or zinc-containing dental cream). Copper supplementation stabilizes neurologic deficits, but reversibility is minimal.

The treatment strategy for copper deficiency is to combine copper supplementation with identifying and removing excess zinc intake.5 The goal is to halt progression of the myeloneuropathy as reversibility may be limited.

Vitamin E

While the primary neurologic deficit in vitamin E deficiency is a spinocerebellar syndrome, there is often a concomitant large fiber sensory-predominant axonal peripheral neuropathy. Vitamin E deficiency occurs in the setting of severe fat malabsorption (eg, biliary dysfunction, cystic fibrosis) or genetic disorders (eg, ataxia with vitamin E deficiency or abetalipoproteinemia). Strategies to treat vitamin E deficiency include improving fat absorption and oral vitamin E supplementation.

Vitamin B6

Vitamin B6 is unusual in that it is associated with peripheral neuropathy either when deficient or in excess. Vitamin B6 deficiency-related peripheral neuropathy primary occurs in the setting of isoniazid treatment for tuberculosis, which can be prevented with concurrent supplementation with vitamin B6. Excess of vitamin B6 can lead to a sensory neuropathy or neuronopathy, which most obviously occurs with megadoses of vitamin B6 (greater than 2 g/d), but has also been reported in patients taking lower doses (50 mg/d) over long periods.6 Since many patients with neuropathy take B-vitamin supplementation, it is worthwhile to ensure they are not taking high doses of vitamin B6 and worsening their disease.

Vitamin B1 (Thiamine)

A progressive axonal sensorimotor peripheral neuropathy due to vitamin B1 (thiamine) deficiency is a part of beriberi syndrome. Atrophic skin changes are also commonly present. The neuropathic presentation of thiamine deficiency is quite varied and may precede the systemic and cognitive symptoms. When thiamine deficiency occurs due to strict malnutrition, there is often involvement of cranial nerves (tongue, facial, and laryngeal weakness), but progressive motor-predominant neuropathy mimicking Guillain-Barré syndrome has also been reported.7 Classic beriberi is very rare in developed countries, where it is often precipitated by gastrectomy; however, neuropathy occurring in severe alcoholics often shares qualities with beriberi (see discussion below). Finally, Wernicke-Korsakoff syndrome in alcoholics is due to thiamine deficiency, and administration of parenteral thiamine supplementation prior to glucose-containing IV solutions can help prevent onset of this condition.
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Alcoholism is one of the most common associations with the development of a progressive axonal sensorimotor peripheral neuropathy. In 2012, 6.5% of Americans age 12 or older self-reported to having five or more drinks on each of 5 or more days in the past 30 days.8 Therefore, it is very important to take a careful history of alcohol use in all patients presenting with neuropathy. Underreporting of alcohol consumption is very common, and approaching this questioning in a nonjudgmental fashion is key. If alcoholism is suspected, it is helpful to have early involvement of trained chemical dependency personnel.

Because alcoholism is common and often has associated malnutrition, it has been difficult to epidemiologically determine whether this association is a direct toxic effect of alcohol,9 a secondary effect of chronic malnutrition and multiple vitamin deficiencies,10 or both. Treatment of alcoholism-associated peripheral neuropathy requires abstinence and a return to a well-balanced diet, which thus treats both possible etiologies. Furthermore, given that alcohol is a known neurotoxin in laboratory studies,11 it is appropriate to counsel any patient with an established peripheral neuropathy, regardless of etiology, on the moderation of alcohol intake. For further information on the neuromuscular complications of alcohol, refer to the article “Neurologic Complications of Alcoholism” by James M. Noble, MD, and Louis H. Weimer, MD, FAAN, in the June 2014 issue of CONTINUUM.

Renal Failure

Chronic renal failure has long been associated with a length-dependent axonal sensorimotor peripheral neuropathy. Referred to as uremic neuropathy, this condition occurs irrespective of the cause of renal failure (eg, diabetes mellitus, glomerulonephritis), and increasing evidence suggests that chronic hyperkalemia may play a role in the development of this neuropathy.12 The pathologic features of uremic neuropathy on nerve biopsy are distinctive, and the characteristic axonal atrophy and secondary segmental demyelination are not associated with underlying conditions that cause renal failure.13 Fortunately, the more severe forms of this condition are rare today, presumably due to early and aggressive dialysis and kidney transplantation. Because of the current rarity of this condition, it is important that other causes of neuropathy be explored in the setting of a patient with neuropathy on chronic dialysis.

Heavy Metals

Exposure to several metals has been shown to cause peripheral neuropathy and may be discovered on laboratory testing of a 24-hour urine sample.14 Lead neurotoxicity may present as a combination of motor-predominant peripheral neuropathy (classically described as wrist-drop) and encephalopathy. There is often concomitant systemic disease, including constipation (likely secondary to autonomic nerve involvement) and microcytic anemia. Fortunately, the incidence of overt lead toxicity with peripheral neuropathy has substantially declined with changes in lead mining practices and decreased human exposure to the major sources in the environment, such as lead-based paint and lead supplements in gasoline. In cases of lead-induced peripheral neuropathy, chelation therapy should be used.15

Inorganic arsenic neurotoxicity may occur from well water contamination, accidental exposure to industrial or agricultural agents, or in the setting of homicidal/suicidal intent. This is to be distinguished from the non-neurotoxic organic arsenic found in some fish and crustaceans, which is often found on urine heavy metal screening. Arsenic neurotoxicity from acute poisoning often occurs 1 to 2 weeks after a severe acute systemic syndrome characterized by nausea, vomiting, and diarrhea. The neuropathy often starts as a length-dependent sensory-predominant painful neuropathy, but in severe forms it may progress to a diffuse sensorimotor polyradiculoneuropathy mimicking Guillain-Barré syndrome (Case 7-2).16 Chronic arsenic exposure can cause an indolent sensory-predominant peripheral neuropathy. Nerve conduction studies in both settings are characterized by slowed conduction velocities. While 24-hour urine sampling will reveal chronic arsenic poisoning, it may not disclose late effects of single or repeated exposures, in which case, it is important to sample hair and nails for arsenic levels.

Thallium was previously used in pesticides and rodenticides, but this has been removed in most Western countries, which, fortunately, has dramatically decreased the frequency of poisoning. Thallium poisoning begins with a severe gastrointestinal illness. In surviving patients, a painful sensory followed by motor neuropathy mimicking Guillain-Barré syndrome occurs within 1 to 2 days, similar to that seen in arsenic poisoning.17 Of note, alopecia, which is a hallmark of thallium intoxication, usually does not occur until 2 to 3 weeks after intoxication. Prussian blue is approved as an oral agent to prevent absorption of thallium.15

The main sources of mercury poisoning come from contaminated fish (organic mercury), industrial mercury salts (inorganic mercury), and vaporized metallic mercury. Organic mercury affects the dorsal root and trigeminal ganglia, causing paresthesia, often before causing widespread CNS dysfunction. Inorganic mercury poisoning primarily causes renal disease, but psychiatric manifestations also commonly occur (eg, Alice in Wonderland’s Mad Hatter was exposed to inorganic mercury in the production of felt hats). Chelation therapy with British anti-Lewisite (BAL) or penicillamine should be tried in patients with nervous system involvement.15

Case 7-2

A 47-year-old woman was transferred to a tertiary medical center for progressive weakness and sensory loss. She was initially hospitalized with severe nausea, vomiting, and dehydration requiring intensive care unit–level treatment. During her recovery from gastrointestinal illness, she began to develop ascending sensory loss and weakness. She was diagnosed with Guillain-Barré syndrome and given a 5-day course of IV immunoglobulin. Unfortunately, she continued to progress and was transferred for further workup and treatment. She had a history of irritable bowel syndrome and reported some baseline numbness in her toes, but otherwise had been healthy. There was no family history of neuromuscular diseases.

Examination was notable for moderate-to-severe length-dependent weakness, multimodal sensory loss, and areflexia. Extensive blood work and CSF analysis was normal (at 3 weeks out from her original illness). Nerve conduction studies and EMG showed a severe length-dependent axonal peripheral neuropathy. Twenty-four-hour urine heavy metals showed detectable levels of arsenic, but were within normal limits. Due to clinical suspicion, hair samples were sent for testing for inorganic arsenic levels, which were found to be very elevated.

Comment. Arsenic neurotoxicity may mimic Guillain-Barré syndrome and is usually associated with severe gastrointestinal symptoms. Urine levels may be normal if tested weeks after acute poisoning, therefore, hair or nail samples may be required for diagnosis when there is clinical suspicion. While cases of arsenic neurotoxicity secondary to groundwater occur, intentional poisoning should be considered when making a diagnosis.

Industrial Agents

Peripheral neuropathy arising from exposure to industrial agents is uncommon in developed worlds,18 primarily due to the restricted (or banned) use of these agents once clear neurotoxicity is established. Where these agents are still used in industrial processes, strict exposure precautions have also reduced the incidence of neurotoxicity. A careful history is warranted as exposure to organic solvents (eg, diketone degreasing agents used in engine shops) is now more commonly encountered in the setting of either personal use or within small businesses that are less carefully regulated than larger industries. Table 7-3 delineates the neuropathies secondary to industrial agents.

Table 7-3

Occupational Exposures of Specific Toxins


Many drugs within a variety of medication classes are associated with peripheral neuropathy. It is important to note that before discontinuing a medication thought to be causing a neuropathy, the patient should discuss the need for the medication and reasonable alternatives with the prescriber. Often, the need for the medication may outweigh the desire to stop it (especially if the association with the neuropathy is in doubt). A list of medications most prominently associated with the development of peripheral neuropathy is included in Table 7-4; for most of these agents, the incidence of peripheral neuropathy is rare.19 Medications causing neuropathy that are no longer in general use have been omitted from this table. Because of the common occurrence of peripheral neuropathy as a dose-limiting side effect of certain chemotherapeutic agents, these are discussed in more detail next in this article.

Table 7-4

Medications Associated With the Development of Peripheral Neuropathy

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Peripheral neuropathy secondary to chemotherapy treatments for cancers affect approximately 30% of patients receiving one of the neurotoxic agents.20 Peripheral neuropathy is one of the major dose-limiting toxicities and frequently decreases the amount of chemotherapy available to treat the underlying cancers. While much of the toxicity relates to dose (and is managed by oncologists), growing evidence also argues for contribution of the patient’s genetics and type of cancer.21–23 Therefore, in patients who develop severe neuropathies in the setting of chemotherapy (especially if not in a classic stocking-glove distribution), it is important to rule out other causes of neuropathy. For example, it has been reported that patients with underlying hereditary neuropathies likely develop more severe chemotherapy-induced peripheral neuropathy.24 Also, there are many reports in the literature about immune-mediated neuropathies in the setting of chemotherapy, which may be a paraneoplastic process or triggered by chemotherapeutic agents.25 Direct compression or invasion of nerve by the underlying malignancy should be considered as well.

Platinum-based compounds (cisplatin, carboplatin, and oxaliplatin) primarily produce a sensory neuropathy/neuronopathy (Case 7-3). Oxaliplatin also has a specific neuropathic syndrome in which patients develop a temporary, but very uncomfortable, cold-induced neuropathic pain in the hands and face. These neuropathic symptoms from oxaliplatin arise from direct interaction with voltage-gated sodium channels leading to altered nerve excitability.26–28 More generally, the platinum-based compounds are thought to cause neuropathy by binding to nuclear and mitochondrial DNA, leading to apoptosis. Neuropathies from platinum-based compounds are also notorious for progressing for several weeks following medication discontinuation, a phenomenon called coasting.

The microtubule toxins, taxanes and vinca alkaloids, produce a length-dependent sensorimotor peripheral neuropathy, likely by disruption of microtubule-dependent axonal transport. Taxanes (paclitaxel, docetaxel) cause stabilization of microtubules, whereas vinca alkaloids (vincristine, vinblastine) destabilize microtubules.

Newer chemotherapy agents approved by the US Food and Drug Administration over the past several years continue to have a frequent side effect of peripheral neuropathy. The proteasome inhibitor bortezomib, used primarily in multiple myeloma, causes a sensory-predominant axonal neuropathy that is frequently dose-limiting. Carfilzomib, a newer-generation proteasome inhibitor, is reported to produce less peripheral neuropathy than bortezomib.29 Both brentuximab vedotin (for refractory large cell lymphoma) and ado-trastuzumab emtansine (for HER2 positive breast cancer) are antibody-drug conjugations where the antibody is cancer specific (anti-CD20 and HER2, respectively), but also have a drug that targets microtubules (vedotin and mertansine), which likely cause the associated peripheral neuropathy.30,31 Likewise, the breast cancer chemotherapeutics ixabepilone and eribulin mesylate, both of which act on microtubules, have been shown to cause a dose-limiting sensory-predominant peripheral neuropathy.32

Case 7-3

A 39-year-old man with a history of testicular cancer presented with new-onset numbness and paresthesia in his hands and feet over the past 2 weeks. He denied any weakness or autonomic symptoms. He completed his final course of cisplatin-based chemotherapy 2 weeks prior to the onset of symptoms, but otherwise had been well.

Neurologic examination was notable for reduced perception of all sensory modalities in the hands and feet (up to the ankles) and areflexia.

His symptoms progressed over the next 2 weeks with sensory loss to the knees and forearms with some gait instability. Extensive blood work and CSF analysis was normal. Nerve conduction study was notable for absent sural sensory nerve action potentials and reduced amplitude median and ulnar sensory nerve action potentials with borderline slow conduction velocities.

A diagnosis of cisplatin-induced peripheral neuropathy was made. The patient had continued mild progression over the next month, which then stabilized. He reported modest improvement 1 year later, but was cured from his cancer.

Comment. Cisplatin-induced peripheral neuropathy usually develops within days of infusion, but may present up to 4 weeks after the last dose of cisplatin. Unlike most other types of chemotherapy-induced peripheral neuropathy, which tend to be length-dependent axonal sensorimotor neuropathies, platinum primarily causes a sensory neuronopathy. This likely contributes to the relative lack of reversibility of the neuropathy after cisplatin discontinuation. Additionally, platinum-based chemotherapy-induced peripheral neuropathies are known to develop the “coasting phenomenon,” wherein symptoms may progress for months after chemotherapy has stopped. Patients may also experience late progression of symptoms when positive painful dysesthesia replace previous negative symptoms of loss of feeling. Typically, even though symptoms have worsened, the clinical examination and electrophysiologic changes are stable. These patients may need to be followed to establish that neuropathy due to a different underlying progressive problem is not present.

Biological Toxins

There are several toxins produced by biological agents that affect the peripheral nervous system, some of which will be covered in the article “Infectious Neuropathies” by Eric L. Logigian, MD, FAAN, and Michael K. Hehir II, MD, in this issue of CONTINUUM.

Ingestion of toxic seafood may be associated with peripheral nerve disorders, often presenting as a syndrome of gastroenteritis and perioral paresthesia. In more severe cases, paresthesia is more widespread with concomitant weakness and occasional cardiovascular collapse. The mechanism of action for all of these toxins is binding of the voltage-gated sodium channel, and symptoms typically resolve within days to months. Ciguatera toxin is produced within dinoflagellate plankton, which then accumulates within fish that consume the plankton up the food chain, which leads to prominent perioral paresthesia, metallic taste, and temperature-related dysesthesia.33 Saxitoxin and brevetoxin B are also produced by dinoflagellate plankton, which are associated with “red tides,” and tend to concentrate in bivalve mollusks and cause more paralysis than ciguatera toxicity.34 Tetrodotoxin is produced within the puffer fish (fugu) ovaries. It is consumed in Japanese sushi, which must be carefully prepared to avoid the potentially fatal toxin.

In addition to neuropathies caused by Lyme disease (carried by Ixodes genus ticks), ticks can produce a “tick paralysis” syndrome that usually affects children under 6. The saliva of three female ticks (Dermacentor andersoni, Dermacentor variabilis, and Ixodes holocyclus) contains a neurotoxin that can lead to a rapidly progressive paralysis, which may include bulbar and respiratory muscles and associated dysautonomia, although sensory systems are spared. Treatment involves supportive care and removal of the offending tick, which leads to rapid reversal of symptoms.

Ingestion of the fruit from the buckthorn plant (Karwinskia humbodtiana), which grows throughout the southwest United States and Mexico, produces a rapidly progressive sensorimotor demyelinating peripheral neuropathy that is very clinically similar to Guillain-Barré syndrome.35 The neurologic symptoms develop 5 to 20 days after fruit ingestion, which may make diagnosis challenging, especially in small children, who are most commonly affected. Of note, the CSF should remain normal in buckthorn neuropathy, and treatment is supportive with slow recovery over many months.


The wide array of deficiencies and toxins that damage the peripheral nervous system highlight its vulnerability, and as illustrated with chemotherapy-induced peripheral neuropathies, even newer agents continue to frequently cause this unwanted problem. While many of these syndromes present as a length-dependent sensorimotor peripheral neuropathy, the more rare presentations with asymmetry and radicular localization require that these peripheral neuropathy causes should be considered in the differential diagnosis of most cases of neuropathy. Fortunately, a thorough history that includes a review of systemic illness, medication changes, and exposures will provide etiological clues in most cases of neuropathy due to vitamin deficiency, toxins, and medications.
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Acquiring a detailed history is crucial to diagnosis of neuropathies caused by toxic agents and vitamin deficiencies.
In a neuropathy with significant asymmetry, polyradicular, or mononeuritis multiplex presentation, other etiologies should be explored further, even in the setting of documented toxicity or vitamin deficiency.
Causes for vitamin B12 deficiency include pernicious anemia, strict veganism, gastric bypass, prolonged antacid use, atrophic gastritis, or diseases of the terminal ileum (eg, resection, Crohn disease).
Copper deficiency may look very clinically similar to vitamin B12 deficiency and should be investigated in parallel in patients with a myeloneuropathy presentation.
Vitamin B6 is unusual in that it is associated with peripheral neuropathy either when deficient or in excess.
Neuropathy due to thiamine deficiency has many presentations, including length-dependent sensorimotor, cranial nerve, and motor-predominant polyneuropathy, all of which may precede cognitive and systemic symptoms.
It has been difficult to determine whether alcohol directly causes neuropathy or if its association with neuropathy is due more to chronic malnutrition and vitamin deficiencies in alcoholics.
Intoxication from arsenic or thallium is preceded by severe gastrointestinal illness, and the neuropathy may mimic Guillain-Barré syndrome.
Toxic exposure from industrial agents may be more likely to occur in people using these agents for personal use or in small businesses.
Newer chemotherapy agents approved over the past several years continue to have frequent side effects of peripheral neuropathy.
Ingestion of toxic seafood may be associated with peripheral nerve disorders, which often present as a syndrome of gastroenteritis and perioral paresthesia.
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