A Few Words...

What is written here is my opinion and personal experience only. I am not qualified to give advice - medical, legal, or otherwise. Please be responsible and do your own research regarding treatments, diets, doctors, and alternative therapies.

Thursday, June 4, 2015

Evaluating Scientific Claims

As an oncology dietitian, it is an integral part of my job to help my patients navigate nutrition and dietary supplement claims they come across through a variety of resources.  While some alternative and complementary therapies have a very low risk of harm and can provide some relief, some can actually be quite dangerous.  Differentiating between something that is safe and effective, safe and not effective, and downright risky can be a daunting task, especially for someone without scientific training.

To make matters worse, anecdotal claims or treatments promoted by (dubious) physicians or others with medical or healthcare credentials can sound so promising, especially when conventional medicine isn't meeting the all of the expectations and needs of the sufferer.  As those of us with Meniere's know, this phenomenon is not limited to cancer patients.

I will be giving a presentation in August on just this subject and will share my slides with you all then.  But in the meantime, consider the following guidelines when evaluating claims regarding treatments and supplements promoted as therapies for Meniere's disease.

It is not lost on me that by promoting cautious evaluation of scientific-sounding claims, that I might be called a hypocrite due to having sought out and chosen to take part in a treatment which is not yet widely known or accepted as standard medical practice in the management of Meniere's disease.  However, between my own training and background, that of my husband, and some of our friends and colleagues, we have been able to sufficiently evaluate and extrapolate from the existing data enough information to form a positive opinion of this treatment option.  And it's this same standard which I encourage others to apply to claims being made for the use of any other particular treatment or dietary supplement.

Sorting out Sources: Guidelines for EvaluatingScientific Information

The goal of this page is to help you evaluate information, specifically scientific information.  This skill is critical not only when conducting research using the internet or traditional print media, but also in helping you sort out claims you may encounter in your daily life.

Be aware of ‘pseudoscience’ (‘false-science’).  Pseudoscientists make claims that may appear scientific, but don’t follow scientific principles.  Distinguishing between science and pseudoscience can be difficult.  When trying to discern whether something is scientific, check the following:

INTEREST

Who is funding the research and who may profit from it?
Biased organizations may give themselves neutral-sounding names.  An organization will often have an interest in the outcome of a study they are funding.

AUTHOR and PUBLISHER

Who conducted the research? Where was it done? Where was it published?
Look at the background of the people involved in the research, if possible. What kind of training have they had? Have they done extensive research in the field? Have they published other papers on the topic? Do others frequently cite them? Was the work conducted at an established facility, which could provide the support necessary to conduct thorough research?

Scientists publish their results in peer-reviewed journals so that others in the same field can critically evaluate their work.  View with suspicion any discoveries that are ‘secret’ or rely on ‘secret formulas’. Results that have been originally published in journals such as Science, Nature, the New England Journal of Medicine, etc. will have been examined more closely, and are therefore are more reliable, than those that are directly announced to the media.

HYPOTHESES

Are hypotheses testable and capable of being falsified?
Hypotheses and theories (even those which cannot be tested directly) should be able to be used to make predictions and allow the collection of evidence to test those predictions.  Often pseudoscientific claims can’t be proven wrong by any possible evidence.  For example, there is no way to disprove the claim that only someone with special powers can sense a certain phenomenon.

There is a large body of knowledge in science that is not influenced by trends in public opinion and is not likely to change.  However, scientific ideas should be capable of changing should new evidence arise. In contrast, ideas in pseudoscience either stay the same (if there is an unchanging idea behind them) or change randomly (if criteria for accepting ideas and rejecting others do not exist).

PROCEDURE

1. Are experiments repeatable? Have they been repeated?
Experimental procedures are reported so that others may repeat them. Valid results can be reproduced by others.  Check to see that there has been more than one study, and that the studies support past research.  One single study may produce results that other studies can’t repeat.  The more independent studies that exist which can support a claim, the more likely it is to be true.

2. Are specific, well-defined predictions made?
Scientists use careful, precise language and make quantitative predictions if possible. Pseudoscientists use vague and imprecise terms that can be interpreted in many different ways, such as the language used in many horoscopes.

3. Are appropriate controls used?
If a drug is being tested, for example, scientists compare an experimental group (getting the treatment) with a control group (not receiving the treatment).

Controls (which should be identical to the experimental group except for the factor being tested) ensure that results are due to the drug itself and not some other factor.  Test subjects should be randomly assigned to either group (‘randomized’). Blind studies (subjects don’t know which group they are in) and double-blind studies (neither subjects nor researchers know which group subjects are in) provide additional safeguards.

4. Was a representative sample used?  Was it large enough? Were enough trials done?
Scientists use samples that represent larger groups.  If only men were used in a study, claims about how the study applies to women would be suspect.

Pseudoscientific or unproven claims will rely on case histories, anecdotal evidence, or personal testimonials (Jane lost 30 lbs. in two weeks with Slim-X!)  While case studies might be a starting point for future research, scientists require many trials combined with statistical analysis in order to evaluate their claims.  Furthermore, ethical scientists wouldn’t reveal the names of people involved in tests.

Sometimes, a statistical claim may be made without reference to the sample size (‘3 out of 4 dentists surveyed’…but how many were surveyed?)  The larger the sample size, and the longer the study lasted, the more confident scientists are about their results

RESULTS

1. Were the results statistically significant?
‘Statistical significance’ measures how often a particular result would occur due to chance alone, assuming that the experiment were repeated many times.  The convention is to say that results are statistically significant if there is a 5% probability or less that the results were due to chance alone.

2. Are logic and statistical analysis used to help distinguish between coincidence (chance), correlation (association), and causation?
Correlation and causation are commonly confused with each other.  For example, ‘people who exercise have a lower risk of heart attack’ is a statement of correlation, but ‘exercise lowers the risk of heart attack’’ is a statement of causation.

It is very hard to prove causation (that A causes B).  In order to do so, one needs to show that A must always be present for B to occur, and that B will always occur when A is present (‘A is both necessary and sufficient cause of B’). An example of how this can be done in science is the use of Koch’s postulates for determining whether a microorganism causes a particular disease:

The organism must be associated with every case of the disease
A pure culture of the organism must be able to be grown outside the body
When introduced into a healthy subject, the pure culture of the organism must cause the disease to occur.
The organism must be recovered from the subject and cultured again.
Because of limits on time, funding, or because of ethical considerations, often the best that can be done is to evaluate a relationship using logic and laws of probability.

When looking for a cause of an illness, scientists would look for large differences between people who had and didn’t have exposure to a suspected cause. They would check to see that those differences are present between groups that would otherwise be at similar risk for developing an illness. Scientists would also check that a logical reason for a suspected relationship exists.

3. Are new ideas or results viewed critically and with skepticism?
Scientists should ideally presume a new idea wrong until it is well supported with evidence.

Pseudoscientists aren’t skeptical of their own results, but are skeptical of the results of others.

Types of Arguments and Persuasive Devices

Certain techniques are commonly used to attempt to convince the reader of the validity of an argument.  Be aware of some of these techniques when you are evaluating a source.

The following types of arguments are discussed in What Science is and How it Works, by Gordon Derry:

1. Straw Man
An argument directed not at someone’s actual position, but at a weaker version (the ‘straw man’) created by the opponent. This weaker version would seem, for example, illogical or irrelevant.

2. Ad Hominem (‘to the man’)
An argument directed at an individual, rather than the individual’s position.  The person themselves is attacked, rather than the evidence or the logic of their argument.

3. False Dilemma
Two choices are proposed, and one of these is more easily attacked.  This leaves the other choice as the only obvious possibility.  However, in reality there may be many other alternatives or complexities which are not addressed.

4. Begging the Question
This type of argument (also called ‘circular reasoning’) assumes the truth of its conclusions as part of the reasoning leading up to the conclusion.

5. Slippery Slope
An argument in which the position argued against is depicted to result in something terrible. The terrible result is then argued against, rather than the position itself.

The following types of persuasive devices are described in Forests: Identifying Propaganda Techniques, by Anderson and Buggey:

6. Bandwagon
‘Everyone else is doing it.’ This technique takes advantage of the desire of many people to feel as though they belong to a group.  The argument is that if most people believe a certain way, then the reader should also feel that way.

7. Slanted Words or Phrases
In this technique, emotionally charged or biased words are used to convince the reader of a certain position (contrast ‘mature citizen’ with ‘old fogy’).

8. Scare Tactics
This technique tries to scare the reader into siding with a particular position. The argument is evaluated on the basis of emotion (fear) rather than logic and reason.

REFERENCES

Aaseng, Nathan. Science vs. Pseudoscience. New York: Franklin Watts, 1994.

American Cancer Society: ACS Newsstand, Interpreting the Science in Scientific Studies (1997), http://www.cancer.org/media/1mar4.html (accessed 7/5/97).

Anderson, Robert, and JoAnne Buggey. Forests: Identifying Propaganda Techniques. San Diego, CA: Greenhaven Press, Inc., 1992.

Arthritis:  Unproven Remedies, Arthritis Foundation, Atlanta, Georgia, 1987.

Derry, Gregory. What Science is and How it Works. Princeton, NJ: Princeton University Press, 1999.

Park, Robert. "Voodoo Science: the road from foolishness to fraud," Oxford University Press, 2000.

Weiss, Noel S. "Distinguishing Cause From Coincidence", Alaska Airlines/Horizon Air Magazines July 1993.

Special thanks to:

Cynthia McClellan, Steve Collins, Nancy Hutchison,
Karen Peterson, Diane Rosman, and Dave Vannet.


Money and Meniere's

Glenn over at Mind Over Meniere's has outdone himself with this post.  He has put together a pretty creative list of ways people disabled with MD might be able to bring in some cash.  For ease of reading, I've copied and pasted the article below. But please considering going directly to the page and subscribing to up-dates.

10 Ways to Make Money From Home with a Chronic Illness

Posted by Glenn


Chronic illness can take so much from so many of us.

We march along enjoying our lives, families, hobbies, passions, and work, until one day, the unthinkable happens. Disaster strikes and you quickly find yourself in an entirely new reality. One where you are suddenly dependent on others and you must be willing to ask for help. The simple chores of daily life become mountains to climb.

But often, the most challenging obstacle is losing the ability to work and provide for yourself and your family. We spend so much of our lives working that it can come to define you. Sometimes, it’s not just a loss of income, but the loss of purpose as well. I know how devastating this can be.

But when your world is turned upside down, it’s important to never lose hope. There are ALWAYS opportunities available; you just have to know where to look.

Regardless of your limitations, there are many ways to generate income, even when you’re stuck at home. With a little bit of effort and creativity, you can find fulfilling work and start making money again.

Here are 10 ways you can start earning money today:

1) Rent out a room in your home:
If you have an extra bedroom in your house, you can rent it out to travelers on Airbnb.com. If you have never heard of it, Airbnb is a website that connects travelers who are looking for a place to stay with people who want to rent out their entire home or just an extra room. It’s a great way to generate extra income and meet some interesting people. Through Airbnb, people can reserve your extra bedroom, just like they would book a hotel room. You can sign up and start today!

2) Rent out your car:
If you are stuck at home and unable to drive, you can easily rent out your car with Relayrides.com. It works just like Airbnb, except you are renting out your car. The service is available in every state across the US except for New York. Plus they offer a $1 million liability insurance policy to keep you covered in case of an accident. You set the price and availability, and Relayrides takes care of the rest.

3) Hire your friends to drive your car with Uber:
Another way to make money with your car is to hire your friends to drive your car for Uber.com. Uber is an innovative company that enables people to make money by driving their car as a taxi. Drivers sign up, and can work anytime they want, simply by launching the Uber app (Android) (IPhone) on their smartphone. Uber connects their drivers with people nearby who need a ride and handles the entire transaction. If you can’t drive yourself, you can hire a friend to drive for Uber with your car and split the earnings. (You will need to add your friend/family member to the insurance policy for your car)

4) Make money watching other people’s pets:
If you still have some degree of mobility, you can make money by dog sitting from your home. Rover.com and Dogvacay.com are two great websites that connect you with people who need pet sitters. If you love animals, this can be an entertaining way to make extra money. Like all of the other companies listed above, both Rover.com and Dogvacay.com handle the entire transaction. Simply sign up, list your availability and you’re all set.

5) Rent out your driveway as a parking spot:
If you live in a big city, near an airport or train station, or near a tourist attraction, you can make money by renting out your garage, driveway, or parking spot to travelers who need a place to park. You won’t make as much money as the other methods listed here, but if you have the space it may worth it. Remember every little bit adds up. You can list your parking spot for rent on JustPark.com and ParkingSpotter.com.

6) Make money buying and selling on Craigslist:
Craigslist.com is an online classifieds page and a great way to buy and sell things locally. If you happen to be a collector or know a lot about a specific type of product, you can make money through craigslist. By finding undervalued products and getting a great deal, you can turn around and resell those products for a profit. Think of your hobbies. Are there things you know a lot about? Maybe you know a lot about baseball cards or vintage record albums. The more you know about a specific type of product, the better you will be at spotting these deals. Sometimes, people even give stuff away for free on Craigslist. It takes time but if you have a good eye for spotting deals, you can make a lot of money on Craigslist.com.

7) Become a paid consultant:
If you were successful in business and think you can help others in the same line of work be successful too, you can make money as a paid consultant. Clarity.fm is a relatively new platform that connects experts with business owners and entrepreneurs who need advice. When you sign up, you set a per-minute price, and through the app, people will be able to call you and consult with you. If you are knowledgeable, it can be a lucrative opportunity.

8) Become a Freelancer and sell your skills online:
If you have ever held a job at any point in your life, odds are you were being paid to put a skill to work. Through websites like Upwork.com, and Fiverr.com, you can sell your skills as a service. All three of these websites connect people who need work completed with the people who have the skills to do the work.

Can you write well? Maybe you are good at editing and proofreading. Maybe you can build websites or do graphic design. If you can do something well, you will most likely be able to offer it as a service to someone else. Some other common examples are creating PowerPoint presentations, translating documents, computer programming, and much more. You can also become a virtual assistant and help people complete various tasks.

9) Write an EBook and sell it through Amazon
Have you ever thought to yourself that you should write a book? Well, it’s easier now than ever before! Thanks to Amazon, you can now self-publish an EBook quickly and easily through Amazon’s Kindle Direct Publishing website. Within 24 hours of publishing your manuscript, you can have your book for sale in the Amazon Kindle store and start earning royalties.

You can even offer a paperback version through another Amazon owned company called Createspace. After you upload your manuscript to Createspace, people will be able to buy a paperback version of your book on Amazon as well. After each order, a copy of your book is printed on demand, shipped to the customer and you get paid a royalty!

You don’t need to write a long book either. A 10,000 – 15,000 word EBook (this translates to a 30-50 page book) can sell amazingly well on Amazon. To put it in perspective, this article is 1,428 words long. The trick is to plan out your idea and write a little bit each day. If you can write 300 words every day, you can finish your book in a month or two.

10) Teach a course online:
You can make a lot of money by creating a class and teaching students all over the world through websites like Udemy.com and Skillshare.com. If you are good at something and think you can teach it to others, this can be a fun and exciting way to generate money. Not to mention, if you can build a great course and a following of students, you can easily sell your students other courses in the future. Take a few minutes and browse the courses offered for sale. It will give you some ideas for courses you may be able to offer yourself!

Conclusion:
If you have been forced out of your job by your chronic illness, it’s a devastating blow, but you still have options. These 10 ideas are a good way to start making money again, but by no means an all-inclusive list. There are more opportunities to make money than ever before and the gatekeepers are gone.

So give these ideas a try! Even if you are still able to work, these opportunities are a great way to generate some extra income on the side.

There is always so much hope. Your chronic illness cannot and will not ever be bigger than your dreams. I wish you the best of luck!

Monday, June 1, 2015

Status Up-Date: Still Well!

I've had a few requests lately for an up-date on my health since starting the Stephen Spring Treatment Protocol (SSTP*).  As of June 11, 2015, I will have been on the treatment for exactly 21 months.

The first 3 months of this treatment were significant only for faster than usual cycling between my usual episodes.  Symptoms during this time were otherwise the same as they had been in the years before I started this, which included severe brain fog, frequent intense disequilibrium, chronic intense fatigue, roaring tinnitus, and vertigo or near-vertigo depending on my limited response to various treatments I had tried up to that point (IT dex, IT gent, antivirals, and allergy shots to name a few).

Between months 3 and 6, I began to notice periods of feeling well which lasted weeks rather than the usual few days.  Symptoms during my episodes were also becoming less intense and shorter.  Amazingly, the episodes started resolving without the occurrence of vertigo or near-vertigo attacks.  That was a first-ever after almost 5 years of vertigo or near-vertigo punctuating my attacks.

During this time, my hearing also improved significantly.  To better illustrate what I mean, my speech discrimination had been consistently declining and hovered between 55%-65% between January 2011 and October 2012.  In January, 2013 it had fallen to 20%!  It had crept back up to 40% a couple of months later and again hovered there.  I started this treatment in September, 2013 and one month later I happened to have a hearing test scheduled and found the results of the speech discrim then were 75% .  Three months later they bounced up to 95%, a level I had not had since the first months after diagnosis in 2009.  Today I still use my hearing aid because in real world settings the tinnitus interferes with my speech discrim.  I would guess that currently, if I had a professional audiogram, that my speech discrim would probably be consistently greater than 80-85%.  I want to say that not everyone I have spoken to on this treatment has had nearly the improvements in hearing that I have had.  I don't know why, but it seems most people are not reporting such drastic hearing improvements.  Though some have observed more conservative improvement.

By the 6th month of treatment, I had developed a whole new symptom which were these short, intense bursts of dizziness.  They were not preceded by aural pressure, changes in tinnitus, brain fog, or generalized fatigue as my dizziness and vertigo had been before.  They would just happen out of the blue maybe 3 to 6 times per day.  Once I realized they would not turn into full-blown vertigo episodes, I learned to live with them  The best explanation for these was they were probably a result of the changing shape of my endolymphatic sac and the resetting of the valve of Bast.  By about the 9th month, they disappeared as quickly as they started.

One year into treatment, I continued to have longer periods, maybe 4-6 weeks, of feeling 95% normal.  These would be sandwiched between symptoms of increased tinnitus, mild-ish brain fog, and fatigue lasting 12-72 hours.  As of now, I would say this is pretty much where I remain.

Today I continue to take the vaccine, albeit at a lower dose in the last few months to see if I can sustain the effects.  I work 20-30 hours per week and am able to do all the things I did before Meniere's without fear of an attack.  I make plans and am able to keep them.  Even when I am experiencing symptoms, they are not so severe that I cannot carry out whatever it is I need to do that day.  Yes, some days are still a little rough, but NOTHING like they used to be.

Overall, I don't take any of this for granted.  I don't believe I am cured, only that this treatment has perhaps corrected, or rehabilitated, my immune system enough to minimize the effects that Meniere's disease has on me.

*SSTP is not for everyone.  It requires commitment, dedication, and for some people a leap of faith.  Also, each person's circumstances, length and extent of disease are unique, so the treatment course may vary from person to person.  Some may require additional medical intervention with prescription medications prescribed by their physician.  I neither encourage nor discourage others from seeking more information about it.  It is a deeply personal decision that should be made with the support of your family and your physician.  It is probably wise to attempt to exhaust all conventional treatments and to consider just how disabling your symptoms are for you.  On the other hand, it would seem reasonable to believe that earlier intervention might mean better, more durable results.  Until there can be large, well-designed studies, we won't know the answers to many questions.  While I am happy to answer general questions, it is best to reach out directly to Stephen Spring at stephen_spring@me.com for specific details of the treatment and to determine if it is right for you.


Sunday, May 31, 2015

A Couple of Cool New Tools

Wanted to take a minute to share a couple of neat tools that showed up in this week.

The first is a thought-provoking questionnaire to help assess dizziness which can be found here.  Check it out!

The second is a super-neat, comprehensive, fillable form for tracking Meniere's developed bn blogger, Glenn, over at Mind Over Menieres.  I could post the pdf, but I imagine Glenn would like to generate some traffic to his site and it's well-worth putting an email address in to get this cool tool.




Monday, April 13, 2015

Is the use of dietary supplements safe?

I have written here at least once before about dietary supplements.  As an oncology dietitian, I hear about and research a variety of supplements people use to treat a variety of conditions, including cancer.  They generally turn to these substances because of something they've heard about from someone they know or read on the internet.

Those of us with Meniere's disease are no different in our desperation to find relief from our symptoms and hope for better health.  However, as is so well-described by Catherine Price in her book Vitamania, dietary supplements are the product of a highly unregulated industry and treated by the FDA in near-opposite fashion as compared to pharmaceuticals and over-the-counter drugs.  Namely, anything classified as a medication, the law states, must undergo years of safety and efficacy testing in real humans before being released for sale to the public.  However dietary supplements are in fact allowed to be sold to the public first, without any safety or efficacy data, and can only be pulled from shelves by the FDA after sufficient evidence, usually in the form of consumer complaints, has revealed that they have caused significant harm or death.  Even in such cases, it is up to the FDA to decide whether or not to pursue a recall and that decision is based in no small part on how much it will cost to launch and pursue an investigation, often running into the millions of dollars and many months or years of legal wrangling.

Harm from supplements may occur immediately upon taking a substance, as was the case with ma huang, aka ephedra, before it was banned for sale in the U.S. in 2004 after its use was linked with heart attacks, strokes, and more than 22 deaths.  But use of other supplements, previously believed to promote good health and longevity, as well as protect from diseases such as cancer, have turned out to also be correlated with potential for serious risk, as in the case of beta carotene and lung cancer, vitamin E and selenium and prostate cancer, and folic acid in the case of prostate cancer.

Now here is an article about a newly published study that has found a strong link between the use of common muscle-building supplements and testicular cancer.  Nice.

Muscle-building supplements linked to testicular cancer: Brown University study

Posted on April 13, 2015 by Stone Hearth News
- See more at: http://www.stonehearthnewsletters.com/muscle-building-supplements-linked-to-testicular-cancer-brown-university-study/cancer-testicular/#sthash.oJoDC5Z6.XNWWYLtY.dpuf

PROVIDENCE, R.I. [Brown University] — Men who reported taking muscle-building supplements, such as pills and powders with creatine or androstenedione, reported a significantly higher likelihood of having developed testicular cancer than men who did not use such supplements, according to a new study in the British Journal of Cancer.

Moreover, said study senior author Tongzhang Zheng, the associated testicular germ cell cancer risk was especially high among men who started using supplements before age 25, those who used multiple supplements and those who used them for years.

“The observed relationship was strong,” said Zheng, who led the study at Yale University before joining the Brown University School of Public Health as a professor of epidemiology. “If you used at earlier age, you had a higher risk. If you used them longer, you had a higher risk. If you used multiple types, you had a higher risk.”

Testicular cancer incidence rose to 5.9 cases per 100,000 men in 2011, from 3.7 cases in 100,000 in 1975, Zheng said. Researchers aren’t sure why.

“Testicular cancer is a very mysterious cancer,” he said. “None of the factors we’ve suspected can explain the increase.”

The study is the first analytical epidemiological study of the possible link between supplements and testicular cancer, the authors wrote in the journal. The work was inspired by mounting evidence that that at least some supplement ingredients may damage the testes.

“Our study found that supplement use was related to a higher risk of developing testicular cancer. These results are important because there are few identified modifiable risk factors for testicular cancer,” said Russ Hauser, professor of environmental health science at Harvard T.H. Chan School of Public Health and a main collaborator of the research.

Testing the odds

To conduct the study, Zheng’s research team conducted detailed interviews of nearly 900 men from Massachusetts and Connecticut — 356 of whom had been diagnosed with testicular germ cell cancer, and 513 who had not. In the interviews, researchers asked the men not only about their supplement use but also about a wide variety of other possible factors such as smoking, drinking, exercise habits, family history of testicular cancer, and prior injury to their testes or groin.

After tallying their data and accounting for all those possible confounders, as well as age, race, and other demographics, the researchers found that the men who used supplements had a 1.65 odds ratio (a 65 percent greater risk) of having developed testicular cancer compared to the men who did not use supplements.

The researchers defined “use” as consuming one or more supplements at least once a week for four consecutive weeks or more.

The odds ratios increased to 2.77 (a 177 percent greater risk) among men who used more than one kind of supplement, and to 2.56 among men who used supplements three years or longer. Men who started using supplements at age 25 or younger also had an elevated associated odds ratio of 2.21, the researchers calculated.

“Considering the magnitude of the association and the observed dose-response trends, muscle-building supplements use may be an important and modifiable exposure that could have important scientific and clinical importance for preventing testicular germ cell cancer development if this association is confirmed by future studies,” the authors conclude in the study.

Future large epidemiologic studies and lab experiments would be necessary to establish a causal link between supplements and testicular cancer.

The study’s lead author is Ni Li of Yale University and the Chinese Academy of Medical Sciences. Other authors are Pat Morey of Harvard T.H. Chan School of Public Health; Theodore R. Holford, Yong Zhu, Yawei Zhang, Bryan A. Bassig, Stan Honig, and Helen Sayward of Yale; Chu Chen and Stephen Schwarz of the Fred Hutchinson Cancer Research Center; Peter Boyle of the International Prevention and Research Institute in Lyon, France; Zhibin Hu and Hongbin Shen of Nanjing Medical University; and Pable Gomery of Massachusetts General Hospital.

The U.S. National Institutes of Health, the National Natural Science Foundation of China, The Beijing Natural Science Foundation, and the Beijing Nova Program supported the research.

- See more at: http://www.stonehearthnewsletters.com/muscle-building-supplements-linked-to-testicular-cancer-brown-university-study/cancer-testicular/#sthash.oJoDC5Z6.XNWWYLtY.dpuf


Sunday, April 12, 2015

Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss

This article was published in September, 2014 in Frontiers of Pharmacology.  I found it a nice summary of different immune approaches that have been tried for sensorineural hearing loss (SNHL), the type of hearing loss experienced by those of us with MD, and the limitations with available agents so far.  (Go directly to the link for references and citations.)  Might it be safe to say that if a successful treatment for SNHL were to be found that it would also address the other symptoms of MD?  It seems a logical conclusion.

Front Pharmacol. 2014; 5: 205.
Published online 2014 Sep 2. doi:  10.3389/fphar.2014.00205
PMCID: PMC4151383

Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss

Takayuki Okano*


Abstract
Sensorineural hearing loss (SNHL) is a common clinical condition resulting from dysfunction in one or more parts in the auditory pathway between the inner ear and auditory cortex. Despite the prevalence of SNHL, little is known about its etiopathology, although several mechanisms have been postulated including ischemia, viral infection or reactivation, and microtrauma. Immune-mediated inner ear disease has been introduced and accepted as one SNHL pathophysiology; it responds to immunosuppressive therapy and is one of the few reversible forms of bilateral SNHL. The concept of immune-mediated inner ear disease is straightforward and comprehensible, but criteria for clinical diagnosis and the precise mechanism of hearing loss have not been determined. Moreover, the therapeutic mechanisms of corticosteroids are unclear, leading to several misconceptions by both clinicians and investigators concerning corticosteroid therapy. This review addresses our current understanding of the immune system in the inner ear and its involvement in the pathophysiology in SNHL. Treatment of SNHL, including immune-mediated inner ear disorder, will be discussed with a focus on the immune mechanism and immunocompetent cells as therapeutic targets. Finally, possible interventions modulating the immune system in the inner ear to repair the tissue organization and improve hearing in patients with SNHL will be discussed. Tissue macrophages in the inner ear appear to be a potential target for modulating the immune response in the inner ear in the pathophysiology of SNHL.

Keywords: resident macrophages, autoimmunity, corticosteroids, cell therapy, molecular targeted drugs

INTRODUCTION
Sensorineural hearing loss (SNHL) is a collection of common auditory disorders resulting from dysfunction of the inner ear, auditory nerve, or the auditory processing pathway in the central nervous system. SNHL comprises a wide variety of auditory disorders including sudden deafness, age-related hearing loss, noise-induced hearing loss, and Meniere’s disease. To date, very little of the SNHL pathophysiology is known because biopsy of the human inner ear is not feasible. Among the purposed mechanisms, immune-mediated SNHL has been introduced and accepted in the last three decades.

The inner ear has been thought of as an immune privileged organ for a long time. The cochlea has no lymphatic drainage, and the blood-labyrinth barrier is tightly controlled to separate the cochlear microenvironment from the circulation. In addition, the concentration of immunoglobulin in the cochlear fluid is 1/1,000 of the concentration in the cerebrospinal fluid (Harris and Ryan, 1984). McCabe (1979) introduced the clinical definition of autoimmune inner ear disease as rapidly progressive bilateral hearing loss that responds to corticosteroid and immunosuppressive therapy. Corticosteroids have been widely used as the first and only regimen to treat virtually all types of SNHL with sudden onset or rapid progression even before McCabe’s report. The anti-inflammatory and immune suppressive functions of corticosteroids led to their common use for hearing loss, especially when inflammation or an immunological disorder is suspected. Despite the common use of corticosteroids for inner ear disorders, our understanding of their role in the pathogenesis of reversible hearing loss remains limited. Steroid-responsive hearing loss does not always indicate an underlying inflammation or immune disorder in the inner ear (Trune and Canlon, 2012). Topical application of corticosteroids in the tympanic cavity has also been reported in patients unable to tolerate systemic treatment due to global adverse effects (Kakehata et al., 2006; Han et al., 2009), and the functional mechanisms of systemic and topical corticosteroid application supposedly differ. Therefore, a better understanding of the inner ear immunology and mechanisms of corticosteroids in the inner ear would enable development of a more sophisticated therapy for SNHL, including immune-mediated inner ear disease. In addition, alternative strategies of modulating immune activity without corticosteroids are desirable for treating certain types of SNHL.

In this review, we will discuss the characteristics and suspected pathophysiology of clinical hearing loss mediated by the immune system. Second, we will describe the current understanding of the inner ear immune system and will explore recent advances in both basic and clinical research of the mechanism of corticosteroid therapy in the inner ear. Finally, we will discuss current and potential SNHL therapies, including treatments targeting immune-mediated inner ear disease.


PATHOPHYSIOLOGY OF SNHL FROM AN IMMUNOLOGICAL VIEWPOINT
The pathophysiology of organ-specific autoimmune disease is believed to be initiated by three primary mechanisms: (i) production of autoantibodies against tissue antigens, (ii) deposition of antigen–antibody complexes in tissue, and (iii) infiltration and destruction of tissue by specific cytotoxic T-cells. To date, the mechanisms of hearing loss in immune-mediated inner ear disease has yet to be determined, and none of the three described pathophysiology mechanisms have been reported in the human inner ear.

Immune-mediated inner ear disease was originally defined by McCabe (1979), who stated that idiopathic bilateral SNHL progresses to deafness over weeks or months, not hours, days, or years, and responds to corticosteroid and immunosuppressive therapy. The term of autoimmune inner ear disease refers to a pathology restricted to the inner ear. The time course of hearing loss distinguishes immune-mediated inner ear disease from sudden deafness or age-related hearing loss. Although this clinical entity is probably immune-mediated as immunosuppressive agents are effective, there is no direct evidence that the condition is autoimmune in etiology because diagnostic biopsy of the human inner ear is not feasible. Moreover, there are no uniformly accepted diagnostic criteria of immune-mediated inner ear disease. The presence of bilateral SNHL of at least 30 dB with evidence of progression in at least one ear on two serial audiograms performed less than 3 months apart is often used as case criteria (Moscicki et al., 1994). Fluctuations in hearing may occur, and immune-mediated disease is one of the few reversible causes of SNHL. Further study is still required to determine the pathophysiologic mechanisms underlying immune-mediated inner ear disease.

The pathology of Meniere’s disease has historically been defined as an inner ear disorder presenting with endolymphatic hydrops. It is well known that some patients with Meniere’s disease show remarkable recovery from fluctuating and refractory SNHL or vertigo following systemic corticosteroid treatment; therefore, an immune-mediated mechanism has been implicated in the pathology of Meniere’s disease (Hughes et al., 1983; Derebery et al., 1991). In a study of patients with Meniere’s disease, immunohistochemistry showed IgG deposition in the endolymphatic sac obtained by surgical biopsy in 10 of 23 patients (Dornhoffer et al., 1993). Alleman reported that 3 of 30 (10%) patients with Meniere’s disease showed a positive serum reaction against proteins extracted from the endolymphatic sac of autopsy samples, and clinical data have shown an association between immunoreactivity and the disease severity (Alleman et al., 1997), suggesting an autoimmune component in some cases of Meniere’s disease. In contrast, other studies report a relationship between herpes simplex virus and the pathology of Meniere’s disease (Bergstrom et al., 1992; Kumagami, 1996). Although it appears likely that an immune reaction is involved in the pathophysiology of Meniere’s disease, the mechanism of endolymphatic hydrops, whether caused by viral infection, autoimmune reaction, or both, remains to be elucidated.

Multisystemic, organ-nonspecific autoimmune pathology may involve the inner ear, leading to secondary SNHL. A limited number of studies have evaluated human temporal bones from patients with autoimmune disease, such as Wegener granulomatosis, polyarteritis nodosa, Cogan syndrome, and lupus (McCabe, 1989; Moscicki et al., 1994). Some specimens showed fibrosis and osteoneogenesis, consistent with the end stage of inflammation. Other bones demonstrated atrophy of the stria vascularis, the organ of Corti, and the spiral ganglion without evidence of inflammation, findings consistent with ischemia. Dettmer et al. (2011) reported that the temporal bones of Crohn’s disease patients with granulomatous inner ear disease demonstrated mild chronic inflammation, poorly defined granulomas, and infiltration of CD68-positive macrophages.

Cytomegalovirus (CMV) is the leading cause of human non-hereditary congenital hearing loss. Approximately 10–20% of children with congenital CMV infection exhibit varying degrees of hearing loss (Barbi et al., 2003; Numazaki and Fujikawa, 2004). However, the pathology of congenital CMV infection within the inner ear is poorly understood. Various animal models have been employed to study the pathology of SNHL caused by intrauterine CMV infection (Woolf et al., 1989; Juanjuan et al., 2011; Wang et al., 2013). Two studies using mouse CMV infection models reported that CMV DNA was detected in spiral ganglion neurons and the stria vascularis (Juanjuan et al., 2011; Wang et al., 2013), suggesting a potential therapeutic target in CMV-induced SNHL. Multiple studies have focused on developing effective vaccines or antiviral therapy for congenital CMV infection. Unfortunately, there is no clinically effective vaccine for congenital CMV infection or CMV-induced SNHL (Arvin et al., 2004).

Several mechanisms have been postulated as the pathophysiology of sudden deafness, including microcirculatory disturbances caused by thrombosis, microtrauma or rupture of endolymph, viral infection or reactivation, and immune-mediated reaction.

One of the main pathophysiology theories of idiopathic sudden deafness is that viral infection or reactivation in the inner ear damages critical structures in the cochlea. Increased serum concentrations of antibodies against CMV, herpes zoster, herpes simplex type 1, influenza B, and mumps have been reported in patients with idiopathic sudden deafness (Merchant et al., 2008; Pyykko and Zou, 2008). Cochlear enhancement on magnetic resonance imaging (MRI) is a potential sign of inflammation in the inner ear and has been observed in some patients suffering from sudden deafness (Stokroos et al., 1998). The inner ear enhancement on MRI disappeared following resolution of hearing loss in 2 of 12 patients with sudden deafness (Mark et al., 1992). Garcia-Berrocal et al. (1997) reported a decreased concentration of both CD4+ and CD8+ cells in patients compared to healthy control subjects, suggesting an abnormal autoimmune response in lymphocyte subpopulations in patients with sudden deafness. In addition, western blot assay showed a response to recombinant human heat shock protein 70, a non-specific heat shock protein, in 19 of 58 (33%) patients with idiopathic SNHL (Tebo et al., 2006). An analysis of 11 human temporal bones from patients with sudden SNHL showed that the morphology of the stria vascularis and spiral ligament were relatively preserved, supporting a viral etiology rather than a vascular insufficiency (Linthicum et al., 2013). These findings suggest that immune mechanisms, including T cell-mediated and antibody responses, are involved, at least in part, in the onset or progression of idiopathic sudden deafness.


EVIDENCE OF THE IMMUNE SYSTEM IN THE INNER EAR
As previously mentioned, the inner ear was believed to be “immune-privileged” and to exclude all immunocompetent cells, except in the endolymphatic sac, for a long time because chronic degeneration without neutrophilic infiltration in the organ of Corti has been described in patients with presbycusis or hearing loss due to chronic noise exposure. However, Rask-Andersen and Stahle (1979) initiated a new era of inner ear immunology by describing intimate contact between the lymphocytes and macrophages in the endolymphatic sac of guinea pigs. This association suggested that two cell types mediated the antigen-presenting process in the endolymphatic sac. The presence of immunocompetent cells and phagocytized antigen within macrophages was also reported in the endolymphatic sac (Harris et al., 1997). These findings revealed the specific role of the endolymphatic sac in antigen processing and immune activity in the inner ear. However, recent studies have demonstrated the presence of immunoreactive cells in other areas of the inner ear even under normal conditions (Lang et al., 2006; Okano et al., 2008; Sato et al., 2008). Lang et al. (2006) reported that bone marrow-derived cells of hematopoietic origin migrate into the cochlea and reside in the cochlear modiolus and the cochlear lateral wall. They also showed that bone marrow-derived cells in the cochlea express ion transporters such as the sodium/potassium/chloride co-transporter or sodium/potassium-ATPase in the cochlear lateral wall, which contains several types of fibrocytes. In a study using bone marrow-chimeric mice that were transplanted with hematopoietic stem cells after receiving lethal systemic irradiation, Okano et al. (2008) demonstrated that bone marrow-derived cells reside as macrophages in the cochlea. They also reported that Iba-1-positive macrophages were continuously and slowly replaced by bone marrow-derived cells from the systemic circulation over several months. Finally, Sato et al. (2008) reported that bone marrow-derived cells expressing CX3CR1, a fractalkine receptor specific to monocytes, natural killer cells, activated T-cells, and tissue macrophages, reside in the spiral ganglion and spiral ligament. In addition, they showed that CX3CR1-positive cells were repopulated in the cochlea over several months. Collectively, these findings indicate that the inner ear harbors immunocompetent cells of hematopoietic origin normally, with most cells likely to be tissue macrophages phenotypically. Although these tissue macrophages are distributed primarily in the spiral ganglion, spiral limbus, and spiral ligament, macrophage-like melanocytes are also observed in the intermediate layer of the stria vascularis (Zhang et al., 2012). These melanocytes reside adjacent to blood vessels and are believed to be perivascular-resident macrophages that contribute to the formation of the blood-intrastrial fluid barrier (Figure ​Figure11).


Distribution of cochlear macrophages. Schematic drawing shows the cross section of the cochlear duct. Cochlear macrophages reside in the spiral ligament and spiral limbus where fibrocytes are located to keep ion exchanges. In addition, macrophages are ...
The role of cochlear macrophages and mechanisms of macrophage migration into the cochlea remain largely unknown. Previous studies demonstrated that injury of the auditory sensory epithelium induces inflammation characterized by macrophage infiltration into the chick basilar papilla (Warchol, 1997; Bhave et al., 1998). A large increase in the number of CD45-positive cells has been observed after noise exposure in the mouse cochlea, suggesting inflammation caused by bone marrow-derived cells (Hirose et al., 2005; Tornabene et al., 2006). The number of cochlear macrophages is also increased after aminoglycoside insult in both the spiral ganglion and spiral ligament (Sato et al., 2010). These findings indicate that cochlear macrophages play important roles in the onset and progression of inflammation after damage to the cochlear sensory epithelium. Macrophages in the cochlea are likely involved not only in the degeneration of the organ of Corti, but also the stria vascularis. Jabba et al. (2006) reported that hyperpigmentation of the stria vascularis and reorganization of marginal cells occurs in Slc26a4-null mice, a mouse model of Pendred syndrome, and is associated with the invasion of CD68-positive macrophages. Similar findings regarding hyperpigmentation of the stria vascularis have also been reported in genetically modified mice (Singh and Wangemann, 2008; Lu et al., 2012). The invasion of macrophages is restricted to the degenerated stria vascularis, suggesting contribution from the cochlear macrophages to degeneration or regeneration of the stria vascularis and the cochlear lateral wall.

The number of cochlear macrophages is also increased by systemic administration of macrophage colony stimulating factor (Csf1), which is one of the primary regulators of mononuclear phagocyte activation. The density of Iba1-positive macrophages is increased in both the spiral ligament and spiral ganglion 1 day after administering Csf1 (Okano et al., 2008), but it is unclear whether the increased macrophage population is due to migration from the circulation or in situ proliferation in the cochlea. Yagihashi et al. (2005) also demonstrated that topical administration of Csf1 ameliorates the degradation of auditory neurons following surgical injury in a rat model. In addition, Csf1 was demonstrated to have neuroprotective properties in an in vitro model of excitotoxicity in hippocampal neurons, suggesting both direct and indirect effects of Csf1 on survival of targeted cells (Vincent et al., 2002). It is unknown whether the activation of tissue macrophages has protective or degenerative effects in the target organ, but control of macrophage activity through Csf1 administration is a potential approach for several inner ear disorders.

Previous reports investigating in situ proliferation of cochlear macrophages are controversial. Using Bromodeoxyuridine labeling, Hirose et al. (2005) reported that cochlear macrophages do not proliferate after acoustic trauma. However, according to the study done by Okano et al. (2008) a subset of macrophages expressed Ki67, suggesting that resident macrophages enter the cell cycle after migration following surgical invasion of the cochlea. Although the precise nature of migrating macrophages is to be determined, cochlear macrophages are most likely responsible for several different inner ear pathologies.


TISSUE MACROPHAGES IN THE INNER EAR
In general, adaptive immune cells play a major role in disease progression, and the innate immune system, primarily monocytes and macrophages, plays a central role in the onset of immune activity. The concept of multiple macrophage activation states is not new, but extending this idea to resident tissue macrophages has garnered increased interest in recent years. Unfortunately, research of peripheral macrophage polarization might not accurately describe their central nervous system counterparts.

Macrophages are derived from monocyte precursors that undergo tissue-specific differentiation and infiltrate the site of infection or injury to produce inflammatory mediators. The cells typically polarize into the pro-inflammatory M1 phenotype and function as an effector of the Th1-mediated immune response. The M1 polarization of macrophages is regulated by several factors including the mineralocorticoid receptor (Lawrence and Natoli, 2011). In the normal course of inflammation, the immune process is controlled, and M1-macrophages undergo apoptosis or switch to the anti-inflammatory M2 phenotype, thereby halting inflammation. However, if the inflammatory response of macrophages is not controlled, it becomes pathogenic, resulting in significant levels of non-specific tissue damage and leading to inflammatory and autoimmune diseases (Wynn et al., 2013). Therefore, macrophage-targeted therapy is extremely relevant in improving the prognosis of inflammatory diseases, particularly inflammation in the inner ear.

Thought provoking observations have been obtained in studies of patients with human immunodeficiency virus (HIV), specifically concerning macrophage function in the inner ear. Monocytes and macrophages are susceptible to HIV infection and are considered a main mechanism responsible for central nervous system infection in areas containing perivascular macrophages and parenchymal microglia (Burdo et al., 2013). Lin et al. (2013) demonstrated that HIV infection is significantly associated with an increased risk of developing sudden deafness in patients aged between 18 and 35 years. In addition, Assuiti et al. (2013) found no direct association between anti-retroviral therapy and hearing loss but stressed the need for future investigation of the causes and association between anti-retroviral therapy and hearing loss. These data suggest that deficiencies in the macrophage and monocyte lineage may lead to dysfunction in the inner ear and highlight the important roles of macrophages in the maintenance of auditory function.

Several surface markers have been used in the animal studies of macrophages to immunohistochemically test their phenotypes and distribution in the tissues. CD68 is a heavily glycosylated transmembrane protein and is a common surface marker expressed in all macrophages (Smith and Koch, 1987; Ramprasad et al., 1996). F4/80 is a member of a gene family that includes the human epidermal growth factor module-containing mucin-like hormone receptor 1 and human CD97, and resides on the surface of a family of cells that includes all well differentiated members of the mononuclear phagocyte system. Although the precise function of F4/80 is not completely understood as F4/80-null mice have no remarkable phenotype, F4/80-positive cells have many common features regardless of their tissue location and are characterized by highly ramified cell shape (Hume et al., 2002). Iba1 is a calcium binding protein specific to macrophages that mediates calcium signals that may control migration and phagocytosis in tissue macrophages (Imai et al., 1996). Reportedly, tissue macrophages in the inner ear express Iba1 in addition to F4/80 (Okano et al., 2008). Csf1r is an alternative surface marker on macrophages and is thought to play key roles in the proliferation, differentiation, and survival of macrophages (Hume et al., 2002). In other categorical systems, the differentiation of monocytes and macrophages is described based on the expression of specific cell markers. If similar markers could be identified in tissue macrophages or cells of monocyte lineage, it may be possible to trace these cells along several different points of the inner ear pathophysiology, including systemically circulating monocytes, migrating monocytes, and resident tissue macrophages.


CORTICOSTEROID THERAPY
Systemic or possibly local administration of corticosteroids is the mainstay of treatment for SNHL, including immune-mediated inner ear disease. However, there are limited prospective data evaluating the appropriate dose, route, and length of corticosteroid treatment. In addition, although many patients experience a short-term response to steroids, the response is generally not sustained (Zeitoun et al., 2005). A prospective, randomized, controlled study in 116 patients with rapidly progressive, bilateral SNHL reported that 57% of patients in the 1 month prednisone challenge showed improved hearing, but adverse effects such as hyperglycemia were observed in 14% of patients (Alexander et al., 2009). A meta-analysis of the management of idiopathic sudden SNHL performed by Spear and Schwartz (2011) reported that intratympanic corticosteroids administered as the primary treatment appeared equivalent to treatment with high-dose oral prednisone. Furthermore, intratympanic administration of corticosteroids potentially recovered some degree of hearing as a salvage therapy. These observations suggest that the local administration of corticosteroids is beneficial through mechanisms distinct from those of systemic corticosteroid therapy.

Despite numerous clinical reports of corticosteroid treatment for SNHL, the spontaneous rate of recovery in acute SNHL complicates conclusions about corticosteroid efficacy. To date, the mechanisms underlying fluctuating SNHL in an immune-mediated inner ear disease are unclear. We know little on how corticosteroids work in the inner ear and which parts of the inner ear are affected during reversible hearing loss. The expression of glucocorticoid receptors in the inner ear is limited to the inner and outer hair cells, the spiral ganglion, and the spiral ligament (Tahera et al., 2006; Meltser et al., 2009). In addition to glucocorticoid receptors, corticosteroids have a strong affinity for mineralocorticoid receptors. The use of systemic mineralocorticoids alone or in combination with glucocorticoids has not been evaluated in humans, but is apparently efficacious in animal models (MacArthur et al., 2008). Because the inner ear requires tight regulation of ion homeostasis in both the perilymph and endolymph, the effect of corticosteroid therapy through mineralocorticoid receptors should be considered in the mechanism of action when treating SNHL. Moreover, there are several questions on the assumptions which clinicians and researchers take for granted. Do corticosteroids only suppress inflammation and immune response in the inner ear? Do corticosteroids affect the inner ear specifically or do the systemic effects of corticosteroids benefit the inner ear disorder? Does immune-mediated hearing loss always respond to corticosteroids? A better understanding of the immune-mediated aspects of hearing loss and specific diagnostic assays would lead to the development of immune-modulating therapy for sudden or progressive SNHL.

McCabe recommended high-dose corticosteroids along with cyclophosphamide therapy for prolonged treatment of immune-mediated inner ear disease (McCabe, 1979). However, the extended follow-up of patients treated with cyclophosphamide revealed potential adverse effects and long-term morbidity and mortality risks of the agent, particularly neoplasm development in younger patients, which limited its use and prompted the search for other immunosuppressive options (Harris et al., 2003; Garcia-Berrocal et al., 2006).

Methotrexate has been used as a sparing treatment to control refractory immune-mediated SNHL. Salley et al. (2001) reported improvement in the majority of 53 patients with immune-mediated inner ear diseases who were treated with low-dose methotrexate. Long-term, low-dose methotrexate therapy appeared to be effective in at least some patients with immune-mediated hearing loss that is refractory to traditional corticosteroid therapy (Matteson et al., 2001). By contrast, a randomized, double-blind, placebo-controlled trial in 2003 of immune-mediated inner ear disease suggested that methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy (Harris et al., 2003).

Azathioprine was also reported as an alternative option in treating immune-mediated inner ear disease, although reports were based on small case series and were inconclusive (Lasak et al., 2001).

According to these findings, systemic immunosuppressives such as methotrexate are effective in some patients with bilateral, progressive, or fluctuating SNHL, which indicates an immune component in the pathophysiology of hearing loss. However, the diagnostic criteria of immune-mediated inner ear disease vary among previous reports. Clinicians and investigators should consider that patients with bilateral fluctuating SNHL do not always have an immune disorder in the inner ear.


RECENT ADVANCES AND FUTURE DIRECTIONS OF SNHL TREATMENT
MOLECULAR-TARGETED DRUGS AND BIOLOGICAL AGENTS

Despite initial optimistic reports suggesting a therapeutic effect of methotrexate, a recent study by Harris et al. (2003) failed to demonstrate its efficacy for long-term management of immune-mediated inner ear diseases as mentioned above. Instead, molecular-targeted drugs have garnered attention of investigators and clinicians in the fields of immunology and audiology due to their specificity against therapeutic targets, resulting in less toxicity and fewer adverse effects.

Etanercept is a fusion protein comprising two recombinant tumor necrosis factor (TNF) receptors linked to the C portion of human IgG1 (Mohler et al., 1993). A retrospective case series by Rahman et al. (2001) examined the response to etanercept in 12 patients with immune-mediated haring loss responsive to high-doses of corticosteroids. Improvement or stabilization of hearing and tinnitus was observed in 91% of patients, suggesting that etanercept therapy is safe and may be efficacious in some patients with immune-mediated hearing loss. By contrast, two studies reported that etanercept has no substantial efficacy in improving hearing loss (Cohen et al., 2005; Matteson et al., 2005). Further studies are needed evaluating alternative regimens that use etanercept or other anti-TNF-alpha agents.

Infliximab is another monoclonal antibody against TNF-alpha that binds TNF-alpha and reduces its activity (Siddiqui and Scott, 2005). A retrospective review of eight patients with suspected immune-mediated hearing loss refractory to conventional treatment examined the efficacy of infliximab on hearing improvement; however, none of the patients exhibited a positive response to infliximab therapy based on objective measurements (Liu et al., 2011). Monoclonal antibody therapy directly targeting cells in the inner ear is unlikely to be effective because the concentration of immunoglobulin is much lower in this region than that in cerebrospinal fluid or blood due to tight regulation by the blood-labyrinthine barrier. Accordingly, transtympanic administration of infliximab was evaluated by Van Wijk et al. (2006) in nine patients with immune-mediated hearing loss. Transtympanic administration of infliximab resulted in hearing improvement and reduced disease relapses, indicating the potential utility of local administration of monoclonal antibody in treating inner ear disease.

Adalimumab was also used to block TNF signaling in patients with immune-mediated hearing loss, but reports were based on a small number of cases (Morovic Vergles et al., 2010).

Rituximab is a genetically engineered chimeric monoclonal antibody against CD20, which resides the surface of B cells. The agent reduces autoantibody production both in circulating and tissue B cells, but does not affect plasma cells. A small pilot study in patients with immune-mediated inner ear diseases was performed evaluating the efficacy of rituximab in treating hearing loss (Cohen et al., 2011). Further evaluation of rituximab is encouraged using a properly designed randomized study.

NUCLEIC ACID THERAPY

Nucleic acid therapy, including delivery of gene constructs to increase or force expression in the targeted tissue, and small interfering RNA to block expression of a specific gene, is a promising approach for treating inner ear disease. However, limited access to the lesion site creates challenges in nucleic acid therapy of the inner ear. Various studies employing animal models utilize viral vectors to introduce the nucleic acid into the inner ear, but there are toxicity and safety concerns associated with this method, including immunogenicity and mutagenesis. Non-viral vectors are advantaged by overcoming these limitations plaguing viral vectors. Although nucleic acid therapy is challenging in the in vivo setting, the development of novel delivery systems could lead to drastic advances in improving the prognosis of patients with SNHL. Obviously, macrophages are a potential target for nucleic acid therapy using novel delivery systems in the inner ear, controlling not only inflammation and degeneration of sensory organs, but also regeneration of the cochlear lateral wall and innervation from the spiral ganglion neurons to hair cells.

DELIVERY OF GENE MODIFIED MACROPHAGES

The last, but not least, the use of genetically modified monocytes or macrophages as vectors should be considered for production of therapeutic molecules or factors that promote regeneration or regrowth of specific structures in the inner ear. This concept is especially well suited for a secreted paracrine or endocrine factor such as a hormone or growth factor. Because the inner ear contains three fluid-filled compartments, secreted factors from genetically modified macrophages could potentially diffuse throughout the inner ear without help from the blood or lymphatic circulation. Although the use of genetically modified cells as vectors of genes or pharmacotherapeutic reagents is in the early stage (Hakuba et al., 2005; Okano et al., 2006; Kesser and Lalwani, 2009), transplantation of genetically engineered cells able to secrete specific metabolic or humoral cues could augment pharmacologic immune modulation in the inner ear. Delivery of genetically modified cells into the inner ear could pose a major challenge because of the anatomical characteristics of the inner ear. Monocytes and macrophages are able to migrate into the inner ear in both pathologic and normal conditions (Hirose et al., 2005; Okano et al., 2008). Thus, the human monocyte lineage could be isolated and cultured ex vivo and genetically manipulated. Intravenous administration of genetically modified monocytes could enable them to reach and migrate into the inner ear, although tissue- or organ specificity could be a potential problem to overcome in clinical applications (Figure ​Figure22).

Schematic depictions of a concept to utilize genetically modified macrophages for the treatment of inner ear diseases. Autologous monocyte lineage is taken from patient’s peripheral blood, and transfected plasmids of targeted gene. After ex vivo ...
Apart from resident macrophages at the disease site, circulating monocytes are continuously recruited to meet the demands of the inflammatory response and the expression of chemokines, cytokines, and cell adhesion molecules. An alternative approach is to facilitate phagocytosis of loaded delivery vehicles by monocytes, which then passively targets the site of disease due to the mounting immune response. The active targeting approach is most attractive and promising if the surface of the delivery vehicle can be decorated with a ligand that selectively interacts with their target receptors. Further research evaluating the use of monocytes as vehicles is desired.


CONCLUSION
In this review, we discussed the involvement of the immune system in the pathology of SNHL, particularly the innate immune system in the inner ear and the pathology of immune-mediated inner ear disease. Recent advances in basic and clinical audiology and immunology research has been rapid. Although there is still much work to be done, we believe that the future of inner ear immunology and SNHL treatment are bright and promising.


Conflict of Interest Statement
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Acknowledgments
This study was supported by funds from the Shimizu Foundation of Immunology and Neuroscience Grant for 2012 and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan and Japan Society for Promotion of Science.

Friday, March 20, 2015

"Gene expression demonstrates an immunological capacity of the human endolymphatic sac"

From the very first day of my journey with Meniere's disease, I have emphatically believed I was having an immunological response to some kind of low-grade, chronic infection.  Doctors kind of acknowledged an immune component to the disease, but really didn't seem to know what to do about it, understandably so since it has been poorly defined up to now.  So when I see studies like this, it makes me want to jump for joy!

Gene expression demonstrates an immunological capacity of the human endolymphatic sac.

Authors
Møller MN1, Kirkeby S, Vikeså J, Nielsen FC, Cayé-Thomasen P.
Author information
Journal
Laryngoscope. 2015 Mar 16. doi: 10.1002/lary.25242. [Epub ahead of print]

Affiliation
Abstract
OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the innate immune system in the human endolymphatic sac. It is hypothesized that the endolymphatic sac has a significant immunological function in the human inner ear.

STUDY DESIGN: DNA microarrays and immunohistochemistry were used for analyses of fresh human endolymphatic-sac tissue samples.

METHODS: Twelve tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample gene expression using adjacent dura mater as control. The expression of genes specific for the innate immune system was determined and results for selected key molecules verified by immunohistochemistry.

RESULTS: A comprehensive overview of expressed genes of the innate immune system was obtained. Multiple key elements of both the cellular and humoral innate immune system were expressed, including Toll-like receptors 4 and 7, as well as beta-defensin and lactoferrin.

CONCLUSIONS: The present data provides the first direct evidence of an immunological capacity of the human endolymphatic sac. At the molecular level, the endolymphatic sac is capable of antigen recognition and processing for initiation of an immune response. In addition, potent molecules directly toxic to invading pathogens are expressed by the sac epithelium. This evidence strongly supports the endolymphatic sac as a significant immunological entity of the inner ear.

LEVEL OF EVIDENCE: N/A. Laryngoscope, 2015.

© 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Sunday, March 8, 2015

Video Presentation About Vestibular Disorders

This video popped up on the Meniere's Disease Team's FaceBook page this morning.  I haven't watched it yet, but the comments are very positive.  Since Meniere's Disease is a diagnosis of exclusion, or a bucket diagnosis, people can be told they have MD when in reality that have one of many other underlying causes for the same set of symptoms.  I think this video will help to distinguish between the subtleties of various vestibular disorders.


Monday, March 2, 2015

A New Blog I Really Like

Mind Over Meniere's popped up on a Facebook feed and after reading through it, I think I found a kindred spirit - one who writes much better than I do and who has a knack for sharing many of the same techniques I've found helpful while learning to live with this disease.  I hope you'll check it out.

Thursday, February 5, 2015

Managing a Vertigo Attack - Stuff I Wish I Had Been Told by My Doctors

Despite seeing a couple of very highly-respected neurotologists and at least two caring ENTs since being diagnosed with Meniere's disease almost six years ago, much of what I know today about the the disease and how to cope with it has come from online forums and Meniere's and hearing loss websites.  Among the contradicting advice I've received over the years involves the use of hearing aids (don't get me started), vestibular suppressants (doctors say don't use them, but the following article - and most sufferers - will beg to differ), and information on the underlying causes (the doctors tend to quickly say 'we don't know', implying they have no idea, but the literature offers at least a few good working theories which the doctors will only talk about if pressed).  Anyway, I digress.

Today I received the following article in my email inbox and found it to contain information I wish I had been given the day I was diagnosed with this miserable disease,  I hope someone finds it at least a little bit helpful during their next attack.

Managing a Meniere’s Attack

By Editor On February 4, 2015


Editor’s Note: Today’s post appeared last month at the Dizziness Depot. We thought it was worth sharing this week at Hearing Views in case you missed it. In today’s post, Dr. Desmond discusses how to manage the debilitating dizzy spells, or “attacks”, caused by Meniere’s disease.[1]
By Alan Desmond, AuD

If you have the flu or a bad cold, the natural response would be to drink fluids and to go to bed until you are feeling better. If you have a bad migraine, lying down in a dark room often provides some relief. Of course, due to the contrarian nature of Meniere’s disease, these activities will most likely make you feel worse. First, I will reprint a short passage from Dr. Tim Hain’s website (I highlighted some text), followed by an explanation of why his advice makes sense.

“How do I manage an attack?”


During an acute attack, lie down on a firm surface. Stay as motionless as possible, with your eyes open and fixed on a stationary object. Do not try to drink or sip water immediately, as you’d be very likely to vomit. Stay like this until the severe vertigo (spinning) passes, then get up SLOWLY. After the attack subsides, you’ll probably feel very tired and need to sleep for several hours.

If vomiting persists and you are unable to take fluids for longer than 24 hours (12 hours for children), contact your doctor. He can prescribe nausea medication, and/or vestibular suppressant medication. He/she may wish to see you or even admit you to the hospital if you are dehydrated. Meclizine (Antivert), Lorazepam and Clonazepam are commonly used vestibular suppressant medications and Compazine, Phenergan or Ondansetron are commonly used medications for nausea. In our practice in Chicago, we commonly prescribe an “emergency kit,” consisting of a small prescription of lorazepam and ondansetron, to be taken sublingually for an acute attack.”

Why a firm surface rather than going to bed?


During a Meniere’s attack, the inner ear is telling you that you are moving. When you are in bed, you have reduced tactile cues about movement and position. Think about how much more difficult it is to maintain your balance of a soft surface like a pillow or foam cushion. The brain is searching for reliable information and tactile feedback, which is much more reliable when received from a solid, ungiving surface. I recommend patients lie down on the floor, up against the wall in a corner and give themselves as much tactile feedback as possible.

Why keep your eyes open and fixed on a stationary target?


The nystagmus (rapid involuntary jerking eye movements) generated from the asymmetric output of your two labyrinths during an attack is what is making you feel as if you are (or your world is) spinning around. By staring at a fixed object, you can slow down the speed of the nystagmus, more so if you look out of the corner of your eye, opposite the direction that the nystagmus are beating. You have to experiment with this: Look out of the right corner of your eye for several seconds, then the left. Make a judgment about whether one side seems better or worse than the other.

This advice incorporates two basic rules of vestibular science:


1. Nystagmus of labyrinthine origin is suppressed by visual fixation –meaning the eye movements (nystagmus) and associated vertigo slow down when the eyes are open and staring at a target.

2. Nystagmus of labyrinthine origin increases in speed when gaze is directed toward the fast phase, and decreases when gaze is directed toward the slow phase –meaning that the eye movements and associated vertigo slow down when the eye is directed away from the direction that the nystagmus is beating. That direction isn’t always predictable and may change during an attack, so you have to experiment with this.

Why take a vestibular suppressant?


Vestibular suppressants may help reduce nausea during an attack.

The nausea is nature’s way of telling you that something is wrong with your vestibular system and that you should probably stay home. You are unsafe to be out hunting or gathering or whatever. Vestibular suppressant medication dampens the information received by the brain from the labyrinths. During a Meniere’s attack, that information is asymmetric, incorrect and making you miserable, so a vestibular suppressant reduces that asymmetry, and reduces the nausea. Of course, the effects will linger after the attack is over and you need to be cautious about sedating effects of the medication if you try to drive. Most people just want to sleep for several hours.

Why take the medication sublingually?


Once an attack starts, medications must be taken sublingually or through a suppository because the vomiting response won’t allow anything to stay down very long.

The bottom line – During an acute Meniere’s attack the inner ear is telling you that you are moving, while the brain, the eyes, and the sense of touch tell you that you are not. This sensory conflict produces nausea and disorientation. Shutting down the labyrinthine response and increasing the visual and tactile feedback will most effectively combat the error signal coming from the affected ear.

Footnotes
Ménière’s disease is a disorder of the inner ear that causes severe dizziness (vertigo), ringing in the ears (tinnitus), hearing loss, and a feeling of fullness or congestion in the ear. Ménière’s disease usually affects only one ear.

Monday, January 26, 2015

Informative Article About Living with Vestibular Disorders

Articles portraying accurate accounts of what it is like to live with a vestibular disorder and their various causes are far and few between.  Most perpetuate misinformation or give false hope.  I thought this article did a good job of touching on the known causes of vertigo and the difficulty diagnosing and treating them.  I encourage you to use the link to go straight to the article itself as it contains an embedded video and links to other articles and stories.  Thanks to Caroline for sharing this from Canada.

Misunderstood and often misdiagnosed, the mystery of vertigoDebilitating chronic dizziness can result from viruses, sports injuries and is difficult to cure

By Meredith Levine, CBC News Posted: Oct 13, 2014 5:00 AM ET Last Updated: Oct 13, 2014 7:59 PM ET

Word went round Janice Mackay's quiet neighbourhood that she was hitting the bottle hard. She'd been seen more than once weaving along the sidewalk in front of her suburban home in Pickering, just outside Toronto, in a sad, drunken stagger.

But Mackay wasn't drunk. As it turned out, her inner ear, the body's balance centre, had been destroyed by medication when she was hospitalized for over a month back in May 2005.

At the time, Mackay was diagnosed with a life-threatening infection in one of her ovaries, and so was put on a cocktail of medication, including an IV drip of gentamicin, a well-known, inexpensive antibiotic that is one of the few that hasn't fallen prey to antibiotic-resistant bacteria.

A few weeks later, the infection was almost gone when Mackay, still hospitalized, suddenly developed the bed spins and vomiting.

Her medical team told her she'd been lying down too long and gave her Gravol, but the symptoms didn't go away.

In a follow-up appointment after her discharge, Mackay was told that the dizziness was a side effect of the gentamicin, and that she would probably have to get used to it.

But she didn't discover the extent of the damage until later when neurotologist Dr. John Rutka assessed her condition and concluded that the gentamicin had essentially destroyed her vestibular system, the body's motion detector, located deep within the inner ear.

After a lengthy legal fight, Mackay eventually settled a civil suit with the suburban hospital that treated her. But nine years later, the spinning hasn't stopped, and Mackay lives with chronic vertigo, the constant illusion of motion.

Her balance is so unstable that she's been unable to get medical clearance to return to work with the City of Toronto, to a job she loved.

A professional hazard

Gentamicin ototoxicity, or poisoning of the ear, is just one way people end up with chronic vertigo. (Though it is one of the worst in that it can damage both sides of the inner ear.)

The problem with gentamicin
In the majority of cases, vestibular damage is the result of a virus. Head injury, autoimmune disease and genetic conditions are also culprits. As are some jobs.

Vestibular problems are a professional hazard for studio sound engineers, soldiers and military trainees who are exposed to bomb blasts, as well as football and hockey players, including Sidney Crosby, who develop chronic vertigo from vestibular concussions.

hi-hadfield-852.jpg
Canadian astronaut Chris Hadfield said he had problems with balance and dizziness on his return to Earth. (Canadian Press)

Even space flight has been implicated. Canadian astronaut Chris Hadfield acknowledged that life back on Earth, after five months of living on the International Space Station, came with dizziness and motion disturbances.

As he told one news organization, "your eye and inner ear are telling you different things."

In the U.S., the National Institute on Deafness and other Communication Disorders estimates that around five per cent of the American population, or roughly 15 million people, suffer from chronic vestibular problems.

There is no comparable Canadian figure, but the usual rule of thumb would suggest that amounts to about 1.5 million Canadians.

A 2009 study published in the Annals of Internal Medicine suggested that 35 per cent of all people aged 40 and older will experience at least some vestibular problems.

In fact, vertigo and dizziness are two of the fastest growing health search terms on Google, according to David Pothier, an inner ear specialist and researcher at Toronto’s University Health Network.

Unfortunately, says Pothier, "vestibular patients are often not taken seriously. They're repeatedly brushed aside as making up their symptoms. But what they experience is very serious and very real."

Often misdiagnosed

The patients who make it to Dr. Pothier's clinic in Toronto have spent, on average, two years bouncing around the health-care system looking for answers before they find him.

Lisa-Tanner
Lisa Tanner, a former college track star from Atlanta, Ga., says she has to hold herself very still mostly to get through her daily routine, and that many doctors wanted to diagnose her with depression. (Meredith Levine/CBC)

And they are among the lucky ones. There is a pronounced shortage of inner ear specialists, in Canada, and most vestibular patients don't end up under the care of a neurotologist.

As a result, their cases are often misdiagnosed as mental illness, and many are then prescribed tranquilizers.

But tranquilizers decrease brain activity, which in turn impedes the regeneration of the vestibular system. So patients on long-term prescriptions often get worse, not better.

Lisa Tanner, a 44-year-old former college track star from Atlanta, Ga., says that most of the physicians she's consulted "wanted to put me on Valium."

See Lisa Tanner's story: 'Don't jump around too much around Mummy'
During a typical consult, Tanner says, she would be asked if she cries frequently. "I'm honest, I say yes because it's hard some days. I do want to just have a cry and then get mad."

But she also tells her doctors that she's not depressed. "I'm not happy about this, but I do want to get better."

Piecing together clues

Diagnosing the cause of dizziness and balance problems is notoriously difficult.

The vestibular system is really just a string of microscopic hairs at the end of cells, inaccessibly encased in bone, beyond the reach of biopsy or current imaging technology.

Accurate diagnosis requires both specialized equipment, which many health-care institutions lack, and specialists willing to invest inordinate amounts of time puzzling over patient charts and test results.

Janice-Mackay-John-Rutka
Janice Mackay, left, talks with Dr. John Rutka, right, head of neurotology at the University Health Network in Toronto and the specialist who finally diagnosed her problem. (Meredith Levine/CBC)



"You have to be like Sherlock Holmes," says Dr. Rutka. "You have to put all the pieces together, find all the clues."

Rutka, a leading international researcher and head of neurotology at the University Health network in Toronto, is the specialist who finally diagnosed Janice Mackay's problem.

For him, one of the rewards of his work is being able to tell these patients, "You're not crazy, you're not psychotic, you're not nuts. Forget what other doctors have told you."

The link to anxiety

But while patients with chronic vertigo are certainly not crazy, there is a complex and fascinating biological link between damage to the vestibular system and the development of anxiety disorders.

Ancient Greek medical texts noted the connection first, but a few millennia on we have yet to fully decode the brain circuitry that connects the two.

"It is difficult to prove, it's difficult to show. But I think it's almost certainly something that's there," says Dr. Pothier.

David Pothier
Inner ear specialist Dr. David Pothier at Toronto's University Health Network says a big problem for vestibular patients is that their complaints are often not taken seriously. (Meredith Levine/CBC)

"When you want to comfort a child, you rock the child. When someone is upset, you rock them gently. People who are under extreme mental pressure often rock themselves."

If there is some kind of biological connection between movement and mood calming, then when the vestibular system — our internal motion sensor — is on the fritz, mood, it would follow, would also likely be affected.

What has been proven is that serotonin receptors, which play a role in mood regulation, exist in the vestibular system, and that there is some link between serotonin levels and vestibular regulation, according to the University of Pittsburgh's Dr. Carey Balaban, a leading researcher in this area.

"If you don't trust your balance system, anxiety is a natural protective process," he explains.

Vestibular patients' blogs and online groups are filled with discussion of anxiety and depression, especially, it seems, when there is little to alleviate the symptoms and patients are sometimes dismissed as fakers.

Joni Church, a 36-year-old video editor in Winnipeg, suddenly developed vertigo six years ago, the cause unknown , and describes struggling with "an inner despair where I felt like my life as I knew it was gone.

"The future for me was just sickness and the inability to do everything I love."

Most chronic vestibular disorders don't respond to medication, and there is currently no way to regenerate inner ear cells, though scientists are working on it.

Joni Church
Winnipegger Joni Church has recovered enough to return to work as a video editor. But it's a tough job for someone with a tendency to vertigo. (Meredith Levine/CBC)

About two-thirds of chronic vestibular patients do improve, although most will never be completely symptom free.

Essentially, these people learn through experience, and through rehab and behavioural therapy, to function as much as possible even when dizzy or off-balance.

Joni Church has recovered enough to return to work as a video editor, but it's a tough job for someone with a tendency to vertigo.

"It does make me a bit ill sometimes," she concedes, but she loves the work so she adapts her life around the condition.

Because her vestibular system has remained faulty, though, Church has been forced to relinquish a second passion: boxing. She was training for her first competitive fight when she became ill.

Next: Rehab, the latest techniques for dealing with chronic vertigo

Saturday, January 17, 2015

Hearing Aids and Balance

Another long absence between posts, sorry, but it just means I've been well and with not too much new to report.  I'm still stable on my current treatment.  But an article I read today prompted me to write this post.

As most of you know, I am a huge fan of my hearing aid (HA).  Based on my own experience and the experiences others have related to me, it seems those of us with Meniere's-related hearing loss tend to be discouraged from getting an HA.  I suspect this is probably not based on any good evidence that HAs have been proven NOT to be beneficial, but more likely on the lack of evidence that they are.  Just about everything I've read or been told on the subject has only been anecdotal.

Understandably, our hearing often does fluctuate, making it a challenge to get and keep the HA properly adjusted.  Also, HAs are expensive so it might seem a waste of money if there's little reason to think it's going to significantly improve one's quality of life,  But in speaking with others with Meniere's disease who have tried an HA and also on what my doctors have said, I'd beg to differ.  The idea that an HA might not be effective for us seems to be based on (1) unrealistic expectations of how an HA can help in ways other than perfecting our hearing (it won't) and (2) not giving the brain enough time to adjust to the HA (in my case, it seemed to take 6-8 weeks for my brain to really rewire and adjust to processing and interpreting sound again).

Anyway, here's an article reporting on a small study which found that HAs might actually improve balance function in people with hearing loss.  After adjusting to my HA, I definitely felt it helped with my balance, as well as echolocation and reducing mental fatigue from straining to hear and process all the sound around me all the time.  I hope more work is done in this area to validate that HAs may do more than just amplify sound for those of us with Meniere's.

Do Hearing Aids Improve Balance?
By Alan Desmond On January 13, 2015 ·

A couple of years ago, I published a post on this blog about a study connecting hearing loss with increased risk of falls. My angle in the post was “Maybe there is a connection, maybe there isn’t, but what should we do with this information?”

Researchers at Washington University of St. Louis decided to investigate whether balance could be improved by treating those with hearing loss with hearing aids. They were specifically interested in whether hearing (in addition to vestibular, visual and proprioceptive) feedback contributed to improved performance on simple balance function testing.

Patients underwent two simple balance tests: the Romberg (eyes closed on foam) and tandem stance (heel to toe) with eyes closed. Throughout the test period, the patients were provided with what is described as “a point-source broadband white-noise sound (0–4 kHz).” Balance was assessed both with and without hearing aids in place.

The study did show that balance performance was improved, both objectively and subjectively, when hearing aid wearers had their hearing aids on and functioning. As noted by the authors “This is a small study. Obviously it needs to be repeated in a much larger study, and we’re seeking funding to do that.”

This is interesting on many levels: It helps support the idea of an association between hearing loss and increased fall risk, and it adds one more potential treatment option in the battle to reduce falls in the elderly. It will be more interesting to see where this research takes us.