HIV Related Neuropathy

Today's video is an Australian view of how HIV can cause neuropathy, whether from the virus itself or the drugs. It comes from PainClinician.com (see link below) and is basically a teaching video for other medical professionals. The difference with most of the other neuropathy videos posted here on the blog, is that if this is what medical students are learning, then we can look at the disease from the point of view of the doctors who treat us. It seems to be full of up to date information and reflects modern medical thinking but apart from the odd scientific term here and there, which may not be so easily understood, the vast majority of the 11 minutes, is pretty interesting to the average neuropathy and HIV patient and explains a few areas which may have previously seemed vague.




http://painclinician.com/video/hiv_related_neuropathy

HIV Related Sensory Neuropathy

Today's post from iasp.files.cms-plus.com (see link below) looks at HIV-related neuropathy and gives the facts, including the depressing thought that they're still not sure why it happens in such large numbers among people living with HIV. Is it the drugs, or is it HIV itself that brings on nerve damage? Does it actually matter for the patient? Not really; what ever the pathogenesis for your neuropathy is, the important thing is dealing with the symptoms when it occurs. The advantage of articles like this is that they are designed for health professionals, so you can be pretty sure that the facts are correct. The problem with neuropathy however, is that there are so many unknown factors that the reader knows there is more information to be uncovered in the future.
 

Painful HIV-Associated Sensory Neuropathy
International Association for the Study of Pain 2014-2015
 
Neuropathic Pain
 
Neuropathic pain (see the fact sheet on “What Is Neuropathic Pain?”) can result from nerve injury or disease affecting the peripheral or central somatosensory nervous systems.
 
Definition 
 
• HIV-associated sensory neuropathy (HIV-SN) is a distal symmetrical polyneuropathy that develops in individuals infected with the human immunodeficiency virus (HIV). The neuropathy is commonly painful.
• The terms HIV-associated distal symmetrical polyneuropathy (HIV-DSP) and antiretroviral toxic neuropathy (ATN) are sometimes used when referring to HIV-SN. HIV-DSP typically describes neuropathy that develops before any
exposure to neurotoxic antiretroviral drugs. ATN describes neuropathy that coincides with starting antiretroviral therapy, and this drug exposure is presumed to be the inciting event. There are no clear differences in the clinical
features of ATN and HIV-DSP.

Clinical Features
 
• Between 40% and 90% of patients report having pain, which often is “burning” in character.
• Other common symptoms include numbness and paresthesia (e.g., pins-and-needles and tingling).
• Symptoms are typically experienced, in common with other distal symmetrical polyneuropathies, in the feet and sometimes the hands.
• Bedside clinical examination typically reveals the bilateral presence of one or more of the following signs in a “stocking and glove” distribution: altered pinprick sensation, absent or reduced deep-tendon reflexes, and an
absent or reduced sense of vibration.

Epidemiology 
 
• HIV-SN is the most common cause of peripheral nerve dysfunction in HIV-infected individuals.
• The neuropathy affects between 30% and 60% of ambulatory HIV-positive individuals, meaning that an estimated 10.5 to 21 million individuals have the neuropathy and are at a high risk of having pain.
• Increasing age and height, any exposure to neurotoxic antiretroviral drugs (e.g., stavudine and didanosine), and worsening infection in individuals not on antiretroviral therapy have been consistently identified as risk factors for
developing the neuropathy.
• Despite the strong association between HIV-SN and neurotoxic antiretroviral use, the neuropathy still affects about 45% of individuals only ever exposed to newer therapies.
• Other possible risk factors include exposure to other causes of peripheral neuropathy (e.g., having diabetes mellitus or receiving isoniazid therapy for tuberculosis infection), being female, and using protease inhibitors.
• Important risk factors for developing a painful HIV-SN include having asymptomatic HIV-SN, exposure to neurotoxic antiretroviral drugs, and having major depression.
• Higher viral load, reduced intraepidermal nerve fiber density, and higher levels of pain catastrophizing are associated with greater pain intensity in individuals with painful HIV-SN.

Impact
• Painful HIV-SN is associated with lower health-related quality of life, lower independence in activities of daily living, and increased risk of having major depression.
• Pain severity is positively correlated with poorer quality of life and with greater dependence, unemployment, and depressive symptoms.
 
Pathogenesis
 
• The pathogenesis of HIV-SN has yet to be to be fully explained.
• HIV-DSP is likely to be a result of interactions between HIV, chemokine-like molecules, and host immune cells (particularly macrophages) that release neurotoxic cytokines. The ultimate consequence of this process is a “die-
back” axonopathy.
• ATN is likely to result from disruption of mitochondrial function by neurotoxic antiretroviral drugs, which contributes to the development of the neuropathy in susceptible individuals. A diagnosis of ATN does not exclude the possibility of pre- or coexisting nerve fiber damage by the mechanisms thought to be responsible for HIV-DSP.
• Genetic studies support a role for mitochondrial dysfunction and inflammation in the pathogenesis of HIV-SN.

Treatment 
 
• There is evidence of a strong placebo response in clinical trials of analgesics tested in patients with painful HIV-SN compared to other neuropathic pain conditions.
• This strong placebo response has complicated attempts to identify treatments that are superior to placebo at relieving the painful symptoms of the neuropathy. Thus, there is a lack of evidence to support the use of many drugs shown to be beneficial in other neuropathic pain states, such as postherpetic neuralgia and painful diabetic polyneuropathy. Only the high-dose capsaicin patch has some evidence of efficacy superior to placebo. 

References 
 
1.
Dorfman D, George MC, Schnur J, Simpson DM, Davidson G, Montgomery G. Hypnosis for treatment of HIV neuropathic pain: a preliminary report.
Pain Med 2013;14:1048–56.
2.
Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, Gelman BB, Vaida F, Collier A, Marra CM, Ances B, Atkinson JH, Dworkin RH,
Morgello S, Grant I. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in
the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol 2010;67:552–8.
3.
Kamerman PR, Moss PJ, Weber J, Wallace VCJ, Rice ASC, Huang W. Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and
in vitro experimental models. J Peripher Nerv Syst 2012;17:19–31.
4.
Kamerman PR, Wadley AL, Cherry CL. HIV-associated sensory neuropathy: risk factors and genetics. Curr Pain Headache Rep 2012;16:226–36.
5.
Phillips TJC, Brown M, Ramirez JD, Perkins J, Woldeamanuel YW, Williams ACDC, Orengo C, Bennett DLH, Bodi I, Cox S, Maier C, Krumova EK, Rice
ASC. Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: a cross-sectional deep profiling study. Pain
2014;155:1846–60.
6.
Phillips TJC, Cherry CL, Cox S, Marshall SJ, Rice ASC. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review
and meta-analysis of randomised controlled trials. PLoS One 2010;5:e14433.
Copyright ©2014 International Association for the Study of Pain

http://iasp.files.cms-plus.com/AM/Images/GYAP/HIV%20Associated.pdf

HEALTHY LIFE STYLE MAY BUFFER AGAINST STRESS RELATED CELL AGING

A new study from UC San Francisco is the first to show that while the impact of life's stressors accumulate overtime and accelerate cellular aging, these negative effects may be reduced by maintaining a healthy diet, exercising and sleeping well.

The study participants who exercised, slept well and ate well had less telomere shortening than the ones who didn't maintain healthy lifestyles, even when they had similar levels of stress," said lead author Eli Puterman, PhD, assistant professor in the department of psychiatry at UCSF. "It's very important that we promote healthy living, especially under circumstances of typical experiences of life stressors like death, caregiving and job loss."

The paper will be published in Molecular Psychiatry, a peer-reviewed science journal by Nature Publishing Group.

Telomeres are the protective caps at the ends of chromosomes that affect how quickly cells age. They are combinations of DNA and proteins that protect the ends of chromosomes and help them remain stable. As they become shorter, and as their structural integrity weakens, the cells age and die quicker. Telomeres also get shorter with age.

In the study, researchers examined three healthy behaviors -physical activity, dietary intake and sleep quality -- over the course of one year in 239 post-menopausal, non-smoking women. The women provided blood samples at the beginning and end of the year for telomere measurement and reported on stressful events that occurred during those 12 months. In women who engaged in lower levels of healthy behaviors, there was a significantly greater decline in telomere length in their immune cells for every major life stressor that occurred during the year. Yet women who maintained active lifestyles, healthy diets, and good quality sleep appeared protected when exposed to stress -- accumulated life stressors did not appear to lead to greater shortening.

"This is the first study that supports the idea, at least observationally, that stressful events can accelerate immune cell aging in adults, even in the short period of one year. Exciting, though, is that these results further suggest that keeping active, and eating and sleeping well during periods of high stress are particularly important to attenuate the accelerated aging of our immune cells," said Puterman.

In recent years, shorter telomeres have become associated with a broad range of aging-related diseases, including stroke, vascular dementia, cardiovascular disease, obesity, osteoporosis diabetes, and many forms of cancer.

Research on telomeres, and the enzyme that makes them, telomerase, was pioneered by three Americans, including UCSF molecular biologist and co-author Elizabeth Blackburn, PhD. Blackburn co-discovered the telomerase enzyme in 1985. The scientists received the Nobel Prize in Physiology or Medicine in 2009 for their work.

"These new results are exciting yet observational at this point. They do provide the impetus to move forward with interventions to modify lifestyle in those experiencing a lot of stress, to test whether telomere attrition can truly be slowed," said Blackburn.

Co-authors include senior author Elissa Epel, PhD, department of psychiatry, Jue Lin, PhD, department of biochemistry and biophysics, both of UCSF and Jeffrey Krauss, MD, division of physical medicine and rehabilitation at Stanford University. Lin, Epel and Blackburn are the co-founders of Telome Health Inc., a diagnostic company measuring telomere biology.

The study was supported by the Baumann Foundation and the Barney & Barbro Foundation. Puterman is supported by the National Heart, Lung and Blood Institute of the National Institutes of Health.

Recognising HIV Related Neuropathy

Today's short post from livestrong,com (see link below) is a somewhat simplistic view of how neuropathy can be related to HIV but nevertheless gives you a good idea of how, why and what. There are relatively few easily readable articles available on why the HIV virus can cause neuropathy, possibly because it's one of the newer areas of study amongst neurologists and HIV specialists. For many years the only link between the two was the knowledge that certain older antiretroviral drugs could bring on nerve damage but now it is accepted that the virus itself can play a major role. The fact that there are over 100 other possible causes, has always clouded the picture.
 

 

Early Symptoms of HIV-Related Neuropathy Sep 14, 2010 | By Jacques Courseault, M.D
 
 


HIV-related neuropathy is a chronic inflammatory polyneuropathy, which describes damage to nerves in the central nervous system or to nerves outside of the central nervous system. The term "polyneuropathy" means that several nerves are involved over the entire body, according to MedlinePlus. This form of neuropathy occurs because the body's immune system overreacts and damages the body's nerves. A patient with HIV neuropathy should be aware of certain early symptoms of this condition.

Numbness and Tingling

According MayoClinic.com, HIV neuropathy can cause numbness and tingling. This occurs because the immune system attacks the nerves, damaging them. The early symptoms that a patient usually experiences are numbness and tingling that may be felt in the fingers and toes, later progressing into the arms and legs. A patient with a known history of HIV who is experiencing a new onset numbness and tingling should immediately schedule an appointment with his physician for treatment.

Weakness

MedlinePlus states that an early symptom of HIV neuropathy is weakness which usually occurs in the arms and hands, or legs and feet. As HIV progresses, the immune system may cause further damage early in the course of the disease. Increasing nerve damage can cause weakness in the extremities, which may make it difficult to perform activities of daily living. In this case, the patient should not hesitate to seek immediate medical treatment so that the proper therapy can be started to prevent further worsening of weakness associated with HIV neuropathy.
 
Pain

Pain is a common early symptom associated with HIV neuropathy, states MedlinePlus. Pain occurs because the body's response to HIV can result in secondary nerve damage which causes pain in the fingers, toes, arms or legs. Pain may be described as burning, achy or tingling. In this case, medications may be prescribed to help a patient cope with the pain. Controlling the underlying progression of HIV will slow the onset of further complications from HIV neuropathy.

References
MedlinePlus: Chronic Inflammatory Polyneuropathy
Mayo Clinic: Peripheral Neuropathy


http://www.livestrong.com/article/244301-early-symptoms-of-hiv-related-neuropathy/

 

African Kids And HIV Related Neuropathy

 Today's post from i-base.info (see link below) is a subject that won't go away until the drug companies stop supplying older and more toxic HIV drugs to third world countries. They do this for two reasons: they're under political pressure to reduce costs for poorer communities and they want to get rid of their supplies of older drugs. D4T, for example is notorious for causing neuropathy as a side effect and it is happening to HIV children more frequently than ever. If you are a neuropathy sufferer, you wouldn't wish it on your worst enemy but to think that young children will be suffering for years on end before a 'cure' or effective treatment arrives, is just tragic. It's a moral question and it's about time governments and pharmaceutical companies got their priorities in order.
 

High prevalence of peripheral neuropathy in children taking d4T in rural South Africa
1 August 2012. Polly Clayden, HIV i-Base

Peripheral neuropathy is a well-known side effect of older nucleosides, particularly d4T, which is still used widely in poor settings.

Although it clearly occurs, this phenomenon is less well characterised in children and it is difficult to assess, particularly with limited resources.

In an oral presentation at IAC 2012, Remco Peters from the Anova Health Institute, Khutso Kurhula Project, Tzaneen, South Africa, showed findings from an evaluation of neuropathy in children in the rural Mopani district. This district is a health priority area in South Africa and the institute runs a nurse managed ART programme in 100 public health care facilities with the support of PEPFAR.

The group used two clinical tools to screen for neuropathy – the neuropathy symptom score (NSS) and neuropathy disability screen (NDS). These tools are feasible for resource limited settings and the NDS only uses a reflex hammer, cotton buds, tooth pick and cold water (to access ankle reflex and perception of vibration, pin-prick and temperature).

It was a cross sectional study of 182 children of median age of 9 years (range 5-15 years) and receiving ART for a median of 2 years (range 2 months to 6.4 years). The majority (86%) received d4T-containing regimens.

Forty-nine (27%) children reported neuropathy symptoms and NDS was positive for 25 children (14%); 43 (25%) children fulfilled the study criteria for peripheral neuropathy.

Co-trimoxazole use was negatively associated with neuropathy OR 0.42, (95% CI 0.20 – 0.88, p=0.019) and there were trends for peripheral neuropathy to be associated with older age and longer time on ART but this analysis is still onging.

Dr Peters included quotes from the children: “My feet are burning, I must take off my shoes in class otherwise I can’t concentrate” from one and, “I can’t sleep at night because of the tingling of my feet; I’m tired during the day” from another.

He concluded that neuropathy is common and frequently undiagnosed in this region and that NSS and NDS are useful diagnostic tools in such settings. Most importantly he added: “Talk to the child!”
comment

d4T associated toxicities have been well documented and screening tools that can be used where resources are limited are welcome.

That children’s experience of adverse events reliant on patient reporting often seems to increase as they get older (and gain a vocabulary) is worth noting.

Co-trimoxazole use appears to be a proxy marker in this study for time on ART/exposure to d4T: children taking co-trimoxazole are much shorter on ART (p = less than0.001). There is not likely to be a specific or direct effect of co-trimoxazole use, but the investigators need to finalise the analysis to be sure about this (Remco Peters, personal communication).

Reference:Peters RPH et al. Clinical screening shows high prevalence of peripheral neuropathy in children taking antiretroviral therapy in rural South Africa. 19th International AIDS Conference. 22-27 July 2012, Washington. Oral abstract MOAB0205.

http://i-base.info/htb/19847

Neuropathy Related To Chemotherapy

Today's short post from blog.dana-farber.org (see link below) may at first glance seem to be very simplistic in that it basically says that you can get neuropathy after cancer chemotherapy treatment. However the link at the end to the presentation and slideshow is very useful and goes into far more detail about how this happens and why. Following the link will provide useful information for those who already have neuropathic symptoms after chemotherapy and for those who may be about to undergo treatment. It's also important to state here that by no means everybody needing chemotherapy will eventually get neuropathy.

Chemotherapy Related Neuropathy: Managing this Nerve Wracking Problem
August 16, 2013 Dana-Farber Cancer Institute

While chemotherapy can kill cancer cells, certain chemotherapy drugs can also cause an uncomfortable and distressing condition that may produce numbness, tingling, and discomfort in the arms or legs. This condition, known as peripheral neuropathy (CIPN), can make it difficult for people to perform day-to-day activities.

Although there is no sure prevention for CIPN, there are ways to control the pain and minimize its effects on quality of life, says Cindy Tofthagen, PhD, ARNP, an assistant professor of nursing at the University of South Florida and post-doctoral fellow at Dana-Farber and the University of Massachusetts.

The condition, which results from nerve damage caused by cancer drug therapies, affects 30-100 percent of patients, depending on the chemotherapy drug used.

“When you’re finished with treatment and the cancer is gone, you think that you’re going back to your normal life and everything is going to be just as it was, but CIPN limits that,” says Tofthagen.

Dana-Farber’s Blum Patient and Family Resource Center recently organized an event with Tofthagen titled “Chemotherapy Related Neuropathy: Managing This Nerve Wracking Problem.” Tofthagen spoke about the risk factors of CIPN and how to manage the condition.

“Hopefully someday we’ll be able to prevent CIPN altogether, but for now you can control the symptoms and continue to live life to the fullest,” Tofthagen says. “It takes time and persistence, and a multidisciplinary approach, but the symptoms can definitely be controlled.”

To view Tofthagen’s presentation, visit the Dana-Farber Slideshare page.

http://blog.dana-farber.org/insight/2013/08/chemotherapy-related-neuropathy-managing-this-nerve-wracking-problem/

Neuropathy An HIV Related Pain Problem

Today's post from paulchristomd.com (see link below) looks at the remarkably high incidence of neuropathy associated with HIV infection. The article mentions a figure of 30% of all people living with HIV, also contracting neuropathy but you will find many experts quoting figures of up to 45% and 50%. Neuropathy can arise from the virus itself attacking the nervous system; or long-term HIV drug use, or any of the other 100 causes that affect the rest of the population. Whatever the accuracy of the statistics, it is clearly a problem for HIV patients and one that is widely underestimated and often poorly treated. Worth a read.
 

Peripheral Neuropathy and HIV-Associated Nerve Pain 
Pain Medicine Specialist, Dr. Paul Christo 2015
 
Most people in the U.S. are aware that HIV (human immunodeficiency virus) causes AIDS, but many might not know that the condition itself and medications associated with HIV/AIDS can end up causing severe pain for those who suffer from it. According to AVERT, a UK-based HIV and AIDS charity, neuropathic pain affects approximately 30 percent of people with AIDS.

Like other serious health issues, such as cancer and diabetes, HIV can cause damage to the peripheral nerves of the body. Symptoms are usually felt in both feet or both hands and can progress up the body in a “stocking and glove” pattern. Minor everyday injuries like a paper cut or sunburn injure these nerves in healthy people. However with a condition like HIV, this nerve damage can lead to burning pain, numbness, or even paralysis. Patients may also feel numbness, tightness, or clumsiness. According to The Peripheral Nerve Center at Johns Hopkins, peripheral neuropathy is one of the most frequent neurological complications of an HIV infection.

On a past episode of Aches and Gains, I spoke with Hotchkiss Brain Institute neurologist and neuroscientist, Dr. Douglas Zochodne. He is a pioneer in the field of nerve regeneration whose work centers around stimulating nerve re-growth in an effort to restore sensory and motor function, as well as ease pain. It’s the work of Dr. Zochodne and other medical pioneers that may give patients who suffer from neuropathic pain of various types some relief and the ability to live a fuller life.

GBS is a condition that can be associated with HIV (and Lupus); it attacks the nervous system and can cause painful, stinging, needle-like sensations along with numbness and weakness. GBS is also referred to as Chronic Acute Inflammatory Demyelinating Polyneuropathy (CIDP) and Landry’s Ascending Paralysis. The cause of GBS/CIDP is unknown, but those with HIV-associated GBS are typically treated similarly to other GBS patients.

Treatment of HIV/AIDS-associated neuropathy varies greatly depending on the level and type of pain. Often, doctors use medicines like gabapentin (Neurontin), pregabalin (lyrica), or duloxetine (cymbalta) and see pain improvement. Peripheral neuropathy caused by certain medications is often treated by reducing the dosage of the drug or completely eliminating it. Though in some cases the damage may be permanent, many patients start to feel less neuropathic pain within a few weeks or months after stopping the medication.

The month of June features two annual observances of HIV/AIDS awareness: National Caribbean-American HIV/AIDS Awareness Day on June 8 and National HIV Testing Day on June 27. For more information on HIV/AIDS neuropathy, visit The Foundation for Peripheral Neuropathy website.

Learn more about nerve pain by listening to podcasts from previous Aches and Gains episodes:
The Mystery of Chronic Inflammatory Demyelinating Polyneuropathy (CIPD)
The Miracle of Nerve Restoration
Painful Diabetic Neuropathy

Each week on Aches and Gains radio show, I outline a new pain source, what causes it, who can be affected, and most importantly, how it can be treated or managed. Visit the radio show page for a complete list of podcasts for past episodes. Tune into Aches and Gains every Saturday at 5 p.m. and 5:30 p.m. on SiriusXM Family Talk Radio Channel 131.

http://www.paulchristomd.com/peripheral-neuropathy-and-hiv-associated-nerve-pain/