“A 9-year-old Georgia boy who developed a rare tick-borne disease got the infection from a blood transfusion, according to a report of his case.

The case is the first time this infection, called ehrlichiosis, was spread by a transfusion, said Dr. Joanna Regan of the Centers for Disease Control and Prevention.”

 “At least now we know we’re not just speculating about the differences between chronic fatigue syndrome and post-treatment Lyme.”

—– EDIT: I posted this before reading the original article (sorry!) and misunderstood the Discover article. There are “biomarkers” that persist post treatment, but this particular study doesn’t demonstrate the existence of the Lyme bacteria itself post treatment —

Original article: Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome

Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, et al. (2011) Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287

“The researchers found that the nature walk and music-driven relaxation changed the expression of 38 genes in these circulating immune cells….  yoga produced changes in 111″

I also looked up the original study  (published in 2012, and open access). On reading more deeply, it appears that the research Salon is referring to is focused on a combination of pranayama (the facet of yoga concerned specifically with breathing) and asana practice (the facet of yoga concerned with poses). They also review past work on the physiological effects of yoga practice. The study tested for gene expression 2 hours after practice but does not shed light on the effects of regular yoga practice over time, or the length of time for which a specific practice has an impact.

Qu S, Olafsrud SM, Meza-Zepeda LA, Saatcioglu F (2013) Rapid Gene Expression Changes in Peripheral Blood Lymphocytes upon Practice of a Comprehensive Yoga Program. PLoS ONE 8(4): e61910. doi:10.1371/journal.pone.0061910

• Retrieving things: Gryffin could help pick things up and bring them to me when I need them. One of the most important: Getting my cane if I realize I need it and don’t have it handy (since I am often just fine, and sometimes have very rapid onset problems, getting a cane and/or a jacket for me could be quite valuable). To help him learn this, I have two first steps: For things that have names, begin teaching the name by putting a treat on it and saying “find name” (for now). For things that don’t have names, he has to learn to pick up first. So I need to give teach him to “take” “hold” and “give” a variety of items with treats. Eventually I’ll be able to point at something or name it and tell him to pick it up and carry it back to me, and maybe even send him down the hall to my office for my cane or jacket if I need it.
• Finding people: This is useful when I am tired and want to ask one of the kids to bring me a drink of water (for example). Teaching it relates to the find part of the last thing. I’ll teach him the name of each family member, and to go to them on command. Eventually we’ll teach him hide and seek and other fun games so he can get someone if I need him to.
• Closing and opening a door: This is useful because I often need to close my door (for private conversations or a nap) and open it (when someone knocks). When I’m feeling tired, it would be nice not to have to get up to do this. To learn closing a door, he first need to learn “touch” which is to push agains something with his nose. Eventually I transfer this to a door by literally taping the thing to the door and letting him practice touching that. Opening a door: This will build on “take” and “hold” by attaching a rope to the door, and teaching him to back up while holding it. Eventually I’d also like to add turning on and off the office light to this.
• Carrying things: He can carry about 1/8th of his body weight, which translates into one laptop and cord on the way to class if I’m having a bad day. Right now we will work on wearing a backpack, and eventually add water bottles for weight.
• Behaving in public: Lots of effort needs to go into this. He still isn’t a great heeler, and he tries to nose new people. He needs a down stay that is totally reliable. And he needs to learn “quiet” which I will probably teach him partly by teaching him “speak” on command :).
• Equipment: My trainer feels it’s important for him to wear a cape to limit attention when he’s “working” at the workplace. I am going to probably transfer some badges I have (“In Training”) and (“Working Dog”) to his backpack so I can use that as his cape. Eventually she recommended getting a handle for balance in those moments when I need it.

I don’t expect to need his help most of the time, but at the moments when I do, it will be a relief to have his help with all of this. And so far he loves every minute of the training, especially when it involves treats!

First off, I am pretty much always experiencing two things at once. Secondly, my order is different.

Denial + Acceptance

I seem to be a master of Cognitive dissonance at the start: Big voice in my head: These initial symptoms will not be a relapse. They WILL NOT BE  A RELAPSE. I will repeat that as often as necessary. Small voice in my head: I’m probably going to have a relapse, but it will be short and I’ll move on. What I say to others: I’m feeling fine. What I tell my husband: I’m having night sweats (or whatever other symptom) so be warned. Hopefully it’s nothing.

Bargaining + Creating A Solution

I go into research mode. My pattern is the same but the outcome is different each time. I come up with some “solution” that will make things better, research the wazoo out of it, start down that road, and if I’m lucky drop it completely because the relapse ends. For example, last time around I researched disability accommodations, this time around I researched canes and low dose naltrexone. The fact that I got to two things (and executed on them both) is probably a hint that this relapse has been longer/worse than usual. This comes with a fair dose of optimism: whatever I come up with, I’m convinced will help. In the case of my new treatment idea, I was stubbornly applying the placebo effect along with hoping it would work for the first four days I took it. On day 5 I could not ignore the symptoms that were coming back, but I’m still going for the placebo effect — though I’ve never experienced one before I’m going to believe this is a herx!

Anger + Self Doubt

I’m currently in the “I want to throw things (if only I had the strength to)” stage. Actually, I do have the strength to sometimes, but at those times I’m neither angry nor depressed so I don’t want to then. It’s when I wake up from a nap and my arms are too weak to even use my cane easily that I want to throw something. This is about when I also allow myself to start wondering if I’m not going to get better, should investigate other diagnosis, and whether I’m contributing enough at work to be useful there, whether I should just stay home and give my kids what they need, and why no one asked me to review any UIST papers or sit on any proposal committees this year.

This doubting is a bit ridiculous considering I am on a program committee and an NSF panel this spring as a reviewer, submitted 8 papers just this Spring (7 to top tier conferences), am co-advising 6 PhD students, teaching a class, helping with the hiring committee and tenure review, and spending plenty of time with my kids. I needed to say (and read) that so forgive me for the self-indulgence. But doubt I do nonetheless. It’s true that at home long walks are limited to when the dog and I both want them, I have lots of kid time, and I can use my energy as much or as little as I want, sleep when I want, play when I want, work when I want. It is so much easier that way, and perhaps that’s the most legitimate reason I phantasize about “just stopping”. On the other hand, at work I am valued for my mind (especially useful to feel and know that when the brain is sometimes fuzzy or difficult), and I contribute in a totally different way than at home. Work may be hard at times but sitting at home feeling sorry for myself while the kids are at school (worst case) would be far harder.

Recovery + Change

I have to believe it will end with recovery, as it always has in the past. A day will come when I get back on my bike, put my cane away and can just be myself again. Or maybe a day will come when I am comfortable in my new skin. But I’m betting on the first outcome. It may make it harder day to day since I don’t truly accept what’s happening to me, but it gives me hope for the future. Besides I get to experience “recovery” almost daily for a few hours here and there. And I am becoming more comfortable using my cane. I don’t use it at home — that’s a space to be myself, relax. But at work, instead of worrying about the attention it attracts I feel the positive energy and support it brings me.

A Good Remedy: Patience + Faith

So where does this all leave me? It seems like forever, but this all started getting bad only at the beginning of March. So I’m a month and a half in, looking at an international trip in a few weeks, realistically this could last 3 months given that travel. Not terrible compared to other relapses, not great either. What I need instead of all of the other things listed above is one simple item: patience. I need to persevere through this as through all the others and wait it out. And I need to keep the faith that this too will pass.

Mechanism:

These facts are primarily taken from the website run by the doctor who discovered its impact on the immune system, Dr. Bihari. To summarize a description of how LDN functions: Naltrexone is an opiate binder and it originally was designed to help heroin addicts (however this was unsuccessful due to the side effects at the 50mg dose used in that context). The side effects are due to it blocking endorphins (which heroin resembles). Endorphins are hormones that are associated with pleasure, but also affect the immune system. Naltrexone helps to increase endorphin production, paradoxically, by blocking it for a brief period. This appears to cause the body to produce increased endorphins in reaction.

This is not the only hypothesis about how things work — for example I found a 2005 article in the journal Medical Hypothesis that was a bit hard to follow but seemed to argue that LDN reduced the formation of a compound that inhibits transportation of a neurotoxin, in MS patients (Agrawal, 2005). On the other hand, a 2008 publication in the same journal conforms more to the Bihari view of the world (Brown & Panksepp, 2008).

Dosage & other issues should (ideally) be discussed with your doctor. I did find the following warnings: LDN cannot be taken along with narcotics, and given its function is not ideal to take with immune-suppressants. It is typically supplied (with a prescription) by a compounding pharmacy. This site advises not taking a “slow release” or “long acting” form  and the same site advises not compounding it with calcium carbonate as a filler.

Clinical trials & other research:

Published studies seem to go back to around 2005, but the drug has been around since about 1984 (Brown & Panskepp, 2008). There are a couple of recent results that are worth talking about. Smith et al. (2013) published a pilot trial with fourteen children with Crohn’s disease showing significant positive outcomes and no serious adverse events.

In other news, the innovative site CureTogether started a trial in 2010. CureTogether takes large scale patient data and pulls out analyses that would otherwise not be possible — not clinically controlled trials but they have discovered new disease mechanisms in the past, for example. Their study replicated the positive findings of a smaller study that was more traditional, both showing benefits for patients with Fibromalgia. That traditional study, Younger & Mackey (2009) was small (10 participants) but very well run (double blind, placebo controlled, within subject). Everyone in the study improved, with some improvements of greater than 30% over the placebo. One possible flaw in the study is that all patients received the placebo first (something they might have guessed at), however the placebo and drug periods were different lengths which might help to mitigate this. The biggest impacts were on pain, fatigue and stress (but not headaches, concentration, and sadness). Patients with the highest baseline sed rate (ESR) were most responsive (.91 correlation) (something the authors say is also true of an earlier Crohn’s trial from 2007 that I haven’t read).

Finally, a follow up study was done with thirty-one fibromalgia patients similar to the first but with a longitudinal design (Younger et al., 2013). This trial was counterbalanced (removing one concern from the prior one) and showed similarly large improvements. The big impacts were on pain and quality of life, with less impact on fatigue or sleep. Also only 32% of participants responded in a large way.

Patient experiences:

For patient experiences I searched primarily for Lyme patients. However I also looked at other diseases. In particular I found a compilation of anecdotes by MS patients (from 2009) that was very interesting, some reports as much as 4 years out from the start of treatment. Given that MS is believed to be misdiagnosed Lyme in some cases, and overlaps Lyme in the symptoms even if not the cause, and that doctors are not all supportive of using LDN for MS, I think this is very interesting.

Lyme patients report known side effects (such as sleep). Some discussion of herxing on it is also found (I have never “herxed” and my LLMD was skeptical of the concept, it is not something I have researched. So I use the terminology of the patient community but retain some skepticism as to what it says about LDN). Some very positive statements about it (e.g. read the last post at the bottom of this page).

Risks:

The risks at low doses seem fairly low. There may be some interaction with other medications (I mention a few above: opiods & immunes suppressors). Thyroid patients should also read up, and there may be some impact on the liver in very large doses. I found comments about it affecting sleep, and causing vivid dreams. I am sure this list is not complete, and anyone taking the drug should research this. Keep in mind that low dose naltrexone should have less significant side effects than the approved (high-dose) version, but similar side effects may be possible.

Decision?

I’m going to try it. The risks are low, and the rest is promising. Some things that might be worth doing before trying it: measuring my sed rate and the endorphin levels in my body, and tracking the impact. Not sure if I will bother — I have reached a point where I care more about whether I feel good and less about the details, or maybe I’m just tired of writing everything down :). An open question for me is how my immune system can on the one hand be highly functional (all winter I’ve had occasional sore throats when the kids got sick but never developed a cold) and on the other hand need a boost. I guess we’ll see what happens :).

References

* means I have read the abstract only

*Smith JP, Field D, Bingaman SI, Evans R, Mauger DT. (2013) Safety and Tolerability of Low-dose Naltrexone Therapy in Children With Moderate to Severe Crohn’s Disease: A Pilot Study. J Clin Gastroenterol. 2013 Apr;47(4):339-45. doi: 10.1097/MCG.0b013e3182702f2b.

Younger, J., Mackey, S. (2009)  Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study. Pain Med. 2009 May–Jun; 10(4): 663–672. Published online 2009 April 22. doi: 10.1111/j.1526-4637.2009.00613.x

Agrawal, Y. P. (2005). Low dose naltrexone therapy in multiple sclerosis. Medical Hypothesis, 6-4, 721-724

Brown, N. & Panksepp, J. (2008). Low-dose naltrexone for disease prevention and quality of life. Medical Hypothesis (2008), doi:10.1016/j.mehy.2008.06.048

*Younger, J., Noor, N., McCue, R., Mackey, S. (2013)

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013 Feb;65(2):529-38. doi: 10.1002/art.37734.

With regard to PCR, tissues were assessed for spirochetal DNA by PCR …. Among the untreated group, 2 animals were positive (Table 1). Here, spirochetal DNA was found in the dorsal root ganglia for one animal, and in the heart for the other. One of the animals of the treated group was PCR positive (Table 1), and in several organs, including the meninges, bladder, spleen, and lungs….

For detection of B. burgdorferi transcript, RNA was extracted from heart and brain specimens. Two of the animals that were not treated with antibiotics were positive, one in heart and the other in brain. Two of the treated animals had detectable spirochetal RNA in the heart, and one additional treated animal was positive for B. burgdorferi RNA in both heart and brain (Table 1). 

The authors go on to discuss a second study. Both studies support the conclusion that Bb can survive antibiotic treatment, at least if it is disseminated (in the late stage) before first treatment (assuming no experimental errors took place).

This study is reassuring evidence that persistent symptoms may actually be caused by Lyme itself rather than an induced auto-immune disease. It is also is depressing, especially given another recent study published in the Journal of Neuroinflammation indicating that Bb is 13 times more likely in Alzheimer’s patients than controls. Details at a great new blog, Hard Science on Lyme.

I can’t really end this post without mentioning the politics of this study, which was originally done in 1998, in order to explore certain things that couldn’t be done in humans (it parallels the well known “Klempner” study, which it contradicts, and which has some serious flaws). What was the hold up? We don’t really know, but an analysis of what we do know about the whole situation can be found at Lyme Policy Wonk. 

Citation: Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, et al. (2012) Persistence ofBorrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE 7(1): e29914. doi:10.1371/journal.pone.0029914

As usual, I find myself trying to make something new of this, because I have to do something. In the past I’ve developed new treatment plans, explored disability accomodations, and explored new doctors. This time around … I went shopping for canes (I had tossed my old one in a fit of hope and because it was falling apart). I’m heading to a conference at the end of April, and I’ve always found “seat canes” to be particularly helpful in that sort of setting, so I invested in a much nicer one than last time around. It arrives Monday, and I hope it will be as nice as it looks online! I’m using a hacked together cane at work right now (an old broomstick with rubber bands so it doesn’t slip!) so I also invested in a very simple wooden cane to replace the broomstick.

Really though, I want something more satisfying to do than shop for canes or try to sleep through it. Lying here in my office (in my lovely zero-gravity reclining chair; another investment in comfort when ill) a few minutes ago I tossed around feeling sorry for myself and even tried to work up to some tears or a good primal scream, but really it just didn’t feel right. It wasn’t going to change anything, after all.  Then I thought about working, but I guess I need a better project in my line up because none of my current ones were appealing enough to pull me out of the haze of pain I was in. So here I am writing a blog post instead (and it is helping :). 

I do feel as though I’m rambling a bit, but I have one last topic to reflect on. I have a colleague who is going through cancer (actually he is caregiver for someone with cancer) and oddly I found myself feeling slightly jealous of them. He is taking time off work for caregiving (not something my husband ever did given that work was already giving me such a big break). He knows approximately what to expect and how long it all will take, and the people around him have a clue as well (i.e. they appreciate the debilitating nature of chemo). Insurance — in network! Negotiating doctors: reading up on the newest research, which the top doctors know about, and can be used to inform the care plan. Prognosis: The longer one is symptom free, the less chance of recurrence (I guess that’s true of Lyme too, but they are at the start of that journey and hopeful that the outcome will be positive). Of course, this also all comes with a significant risk of death, something that I am grateful not to be facing. Even so, it sure would be nice if Lyme disease was as mainstreamed and well understood.

So having used this blog post indirectly to complain about how lousy I am feeling and how unfair it all is, especially in comparison to people with cancer (and yes, I am being sarcastic, at least in part), I suppose in the end I have gotten my “feeling sorry for myself” out. Thanks for listening.

I remember the days and days of being grateful for feeling well when I first came out of the worst of my Lyme disease (which I re-experience after each relapse), but today I am grateful for feeling lousy! And laughing at the very idea that a cold is a reason to give thanks.