“I Fight It”

As has been reported previously in this blog, I am increasingly looking like a walking question mark.  So it was not surprising when I was recently asked if I had scoliosis (that is, curvature of the spine).  I  told my friend that no, the stooped, twisted posture was a, ummm, gift from my Parkinson’s diagnosis.  She told me she asked because she herself had dealt with scoliosis for many years.  I asked her what she did about the scoliosis, expecting that I would hear about some new exercise.  Instead, she responded, simply: “I fight it.”

I think that will  be my mantra for the new year:  “I fight it.”  This year that is just ending has been challenging as I have “fallen off the cliff” and moved on to the next stage of Parkinson’s disease.   The honeymoon is clearly over.

I have three therapeutic avenues to deal with Parkinson’s symptoms.  One is medication.  I have now gone through eleven different combinations since the beginning of the year, and I’m about to try one more tweak.  I started this experimentation with a blog about my pharmaceutical fairy godmother (“Bibbidi Bobbidi Boo”).  Alas, there is no magic wand.  And as my neurologist put it, my worst symptom (crooked posture) is “not helped very much  by pharmaceutical therapy”.

Therapy #2 is exercise.  There’s an old gag that the definition of insanity is doing the same thing and expecting different results.  I think in my case it’s not doing the same thing and expecting different results.  I have returned to the personal trainer I worked with last year on correcting my posture.   I rush home after each session and take detailed notes before I forget her expensive advice.  Yesterday, I read through my notes from last year’s sessions.  Hmmm….they sound a lot like my notes from….this year’s sessions.   And hmmm….I’m doing some of her advice, but not all, and not very consistently or intensely.   I think this is the biggest area to apply the mantra:  “I fight it.”

 Therapy #3 is….what do I call it?  Mental health challenges, I guess.  An example is swing dance lessons.  I skipped the last two weeks because my back was too sore.  But this week I was determined to show up at the lesson, since this is my last opportunity to practice before the dance party on New Years Eve.  Tonight, the dance instructor  gave me some invaluable tips, pointing out that when I turned under my partner’s arm, my frame tended to collapse, and I was looking at the floor, not at my partner.  Gosh, you mean my posture is crooked? What a surprise!  And you know what I’m going to do about my crooked posture at that New Year’s dance party?  “I fight it.”

 

Pinky’s Passion

Pat “Pinky” Erickson, complete with pink hair and pink festive hat

A quick shoutout to Pat “Pinky” Erickson.  She and her family have raised around half a million dollars over the last ten years for Parkinson’s research and support.  That’s right – half a million dollars.  They have achieved this feat through several creative events —  fashion shows,  rock concerts,  auctions.  I had the honor of being invited to a holiday dinner party, their 10th annual fund raising dinner, which included a live auction.  I have to say, knowing the Ericksons’ fundraising success, I imagined the guests would all be extremely wealthy, holding their flutes of Dom Perignon as they gazed out at a million-dollar Puget Sound view.  Nope.  No champagne, no view, just a lot of regular folks who are very generous.   I asked Pinky’s daughter how much they usually raised from these dinners.  She estimated about $20,000, which anyone who has run a charity auction could tell you is a very healthy amount.   I don’t know what the final amount was for this event, but, given the bids I was hearing, I think they will meet or exceed that estimate.  Good work, Pinky and your family, and thank you!

PS.  Want to donate to  Pinky’s Passion?  Check out her website.

The Tale of the Contursi Kindred

The Contursi Kindred – Sounds like a Dan Brown thriller, doesn’t it?  But it actually refers to an important early breakthrough in Parkinson’s research.  This research tale is well told by Jon Palfreman, an excellent science writer who started writing about Parkinson’s after he got a diagnosis himself.   This blog post pulls from  his 2015  book Brain Storms: The Race to Unlock the Mysteries of Parkinson’s Disease.

The tale starts in 1986 when the brother of a Parkinson patient  approached New Jersey neurologist Larry Golbe and thought he too might have Parkinson’s.   Intrigued that two brothers both exhibited Parkinsonisms (not usually a genetic disease), Golbe dug further and found six relatives with Parkinsonisms.  He also learned the family had immigrated from a small town in southern Italy,  Contursi.  Months later, Golbe had another Parkinson’s patient of Italian descent — whose family also had immigrated from Contursi.

Ding!  The light bulb went on.  Although Parkinson’s does not typically run in families, Golbe realized he might have stumbled on a rare exception: a family “kindred” that passed the illness from generation to generation. He called his boss and mentor Roger Duvoisin, and together they embarked on an international journey of medical detective work.

After some exhaustive family tree research going back 12 generations, the doctors found that a mind-boggling 61 recent descendants out of 574 had Parkinson’s.  Descendants had a 50-50 chance of getting Parkinson’s.  There was obviously something genetic going on.

This was in the early 90s, as genetic research was starting to ramp up.  Finding a gene mutation was challenging – The New Jersey scientists collected blood samples from Contursi descendants and searched unsuccessfully for more than seven years. Then, in 1995, Zach Hall, who at the time was director of the National Institute of Neurological Disorders and Stroke (NINDS), suggested they share their Contursi blood samples with other investigators.  A collaboration was formed between the New Jersey researchers and two scientists then at the National Institutes of Health: Bob Nussbaum, a clinical geneticist with advanced molecular biology training, and Nussbaum’s colleague Mihael Polymeropoulos.

Within nine days, the NIH scientists had narrowed their search to one stretch of chromosome.  But it took nine more months and running the sequence against GenBank, an open-access genome database, to get a hit:  The gene was SNCA which coded for a protein called alpha-synuclein.  A single base change in the gene’s million-letter genetic code produced a mutant form of the protein, which caused affected members of the Contursi kindred to develop Parkinson’s.

The rare Contursi mutation does not show up in the DNA of regular Parkinson’s patients, but the role of alpha-synuclein has proved to be a vital clue in the wider war on the disease.  For starters,  those nasty Lewy bodies that clog the brains of Parkies are made up of — you guessed it — alpha-synuclein.  For more about this bad-boy protein, check out a previous blog.

Is Parkinson’s genetic?  Since the 1997 discovery of the alpha-synuclein mutation, some 18 potential genetic forms of Parkinson’s have turned up, involving another 10 or so genes.  But most People with Parkinson’s (like me) have no family history of Parkinson’s.  Perhaps there is something deep in my genome that predisposed me to get Parkinson’s — triggered perhaps by some sort of external factor.

Who will take care of us?

I recently read an article about a large study in China suggests a link between their really bad air pollution and impairment of cognitive skills.  This was disturbing, but more alarming was a throw away statistic in the article.  The article mentioned that “China already has the world’s largest population of people with dementia, as of 2013 about 44.4 million, and expected to rise up to 75.6 million by 2030.”  (This is from a report in 2013 by Alzheimer’s Disease International, a nonprofit based in Chicago.)

Wait – you’re telling me there’s 44.4 million people who need care in a country full of families with only one precious boy?  (It’s sexist I know, but I don’t think the precious boy will be the one wiping the oatmeal off of Grandma.)  China currently has an estimated population of 1.4 billion, so, whipping out the calculator, that’s 3% of the  Chinese population with dementia – a sizeable percentage.

This doesn’t include Chinese people with Parkinson’s.  The China Daily reports, “In China, it is assumed that more than 2.5 million people are living with Parkinson’s disease today. With the worsening trend of aging, the figure will surge to about 5 million in 2030 accounting for more than half of the world’s patients at that time.”  Not to sound too callous, but 2.5 million is a rounding error when your population is over a billion people.  Adding in the Parkies, this still comes to over 3% of the Chinese population who  presumably need or will need fairly constant and intensive caregiving.

How does this compare with the US?  The current estimated US population is 326.8 million.  The number of people with Alzheimer’s is estimated to be 5.7 million.  The number of people with Parkinson’s is estimated to be 1 million.   So, doing the math, about 2% of the US population has Alzheimer’s or Parkinson’s and presumably either requires caregiving now or will in the future.

Here’s a few more sobering stats from the Alzheimer’s Association website:
–16.1 million Americans provide unpaid care for people with Alzheimer’s or other dementias.
–These caregivers provided an estimated 18.4 billion hours of care valued at over $232 billion.

Knock on wood, I’m far away from needing caregiving.  I am fortunate to be married to a man who is only 9 months older than me, with no health problems or family history of dementia.  So hopefully, when the time comes that I need care, my husband will be the caregiver (or “care partner”, a more politically correct and accurate term).  And if I need more care resources, I hope that they will not have all been hired by China!

The Board Game of Drug Development

Sir Alexander Fleming

I think we all nurse a romantic vision of a Parkinson’s cure.  The tale of Sir Alexander Fleming returning from vacation in 1928 and finding a mold that would become penicillin is a true story, but even in 1928, this simplistic story leaves out hundreds of researchers, government scientists, drug manufacturers, and most fundamentally, lots of money.

The complicated board game that is drug development is illustrated by the announcement this week of a successful safety test in humans of a LRKK2 inhibitor.  This was announced at the annual Michael J. Fox Foundation (MJFF) scientific conference by Denali Therapeutics.  Sounds kind of ho-hum, doesn’t it?  But this development was described as a  “milestone moment” in the announcement’s headline.

Let’s break down the steps in the board game:
–First, LRKK2 was discovered about 15 years ago to be one of the principal gene mutations that causes Parkinson’s.  About 15% of the Parkinson’s population has genetically caused Parkinson’s.  So a drug that inhibits the bad actions of LRKK2 would be handy.
–Second, drugs are tested on animals before they are tested on humans.   When the LRKK2 inhibitor was tested on animals a couple years back, side effects caused worrisome changes in lung tissue.
— SCREEECH!  If you were a drug company, would you want  to continue testing this drug?
–MJFF intervened to keep this drug development moving.   MJFF brought together three competing companies developing LRRK2 drugs for Parkinson’s through the LRRK2 Safety Initiative. The three companies pooled their knowledge and evaluated what might have gone wrong.   The Initiative demonstrated that LRRK2 inhibitors were safe for human testing, allowing continued investment and research.  MJFF also ponied up some of the funding for testing.
–The first step in drug testing on humans (Phase I) is safety testing,  In other words, before we even test its efficacy, is this drug safe for humans?  What are the side effects?
Denali did not find “statistically significant differences” in side effects between the placebo group and groups receiving varying doses. 

So what’s next?  Phase II testing — this is moving into testing the efficacy of the drug.  None of the test subjects in the Phase I testing had Parkinson’s.   Phase II  subjects will need to have not just Parkinson’s but the LRKK2 gene mutation.  Fortunately, MJFF has been working with consumer genetics company  23andMe to build up a database of Parkinson’s genetic volunteers.   I need to double check because it was a couple years ago, but I believe my relevant genetic information is in this database.  Nope, sorry, I don’t have LRKK2 mutation or any of the other gene mutations associated with Parkinson’s.

 

 

 

 

 

 

The Renaissance Man

What do the Seahawks football team, Jimi Hendrix, the Cinerama movie theater, rockets to outer space, and mouse brains have in common?  They were all passions of Paul G. Allen, who died at  65 on October 15 from complications of non-Hodgkin’s lymphoma.   And since he amassed a fortune in the billions from being a Microsoft founder, all of these passions (along with many, many  other areas) were also substantial investments.

I am grateful for all the investments Paul Allen made in my hometown of Seattle.  (Well, the MoPOP Museum, originally intended to honor Jimi Hendrix, maybe not so much — it still looks like a plane crash off I-5.)  But the investment I am particularly grateful for is the Allen Institute for Brain Science, founded in 2003.  Allen plowed what is amusingly referred to as “seed money” in the Wikipedia entry – a cool $100 million – into this institute.   The first project was indeed an atlas of the mouse brain genome.  In 2010, the Institute launched the Allen Human Brain Atlas — mapping all 86 billion of those neurons.

The Institute is not researching Parkinson’s or other specific neurological disorders, but it is doing the fundamental neurological research necessary for someday finding a cure.  For instance, a current program is what the Allen Institute website delightfully calls “BrainTV” — ultimately being able to see what is happening in the brain as it happens.  Imagine the progress we could make in fighting Parkinson’s if we could see what happens to dopamine when it encounters a clog of bad-boy alpha-synuclein protein.

So thank you, Paul Allen.  Seattle and the world will miss you.

Bozo approaches the cliff

I have asked my neurologist several times “When do I fall off the cliff?”  In other words, when do things get really bad?  He always smiles and in his positive way, assures me that Parkinson’s doesn’t progress like that.  I’ve never fully bought into that response, and lately, I feel like I’m teetering on the edge of that cliff.

Case in point:  The community 5k run.  I’ve “run” this for a few years now (mainly walking, but last year my time was an almost respectable 46 minutes).  This year, I decided to sign up back in June even though the event wasn’t until September 30, so that I would be less tempted to weasel out of it at the last minute.  And I knew it was a mere two days after a 4-week trip abroad, but I figured I would be doing lots of hiking and walking on both the September trip to the Dolomites and my August trip to the Canadian Rockies.  Nope.  My walking has deteriorated so that after an hour or so, I need to lie down to “reset” my back which is curved over like a question mark.   As you can see, I dragged myself to the starting line, but the course conveniently went close to my house and I exited after about a mile. Now I’m wondering if I’m going to be able to lead the monthly walk I do for a community walking group. 

So what’s going on?  I am convinced that I do not have the right pharmaceutical combination.  Back in March, I decided it was time to move up to the heavier ammo of carbidopa/levodopa (that is, “fake” dopamine) from the dopamine agonist I was taking (makes your remaining dopamine work better).  My reasons were that I was tremoring more, had difficulty turning over in bed, and most impacting, could not shake my stooped-over posture.  I have now gone through four different combinations, thought I had hit the “sweet spot” but have deteriorated so quickly that I think it’s the drugs not the disease.  I have all these same symptoms — but worse now.  When I try to straighten up, I bob and weave like …..a Bozo doll.    I first felt like Bozo when my drug combination was higher than it is now, making me suspect I may have too much levodopa…but then again, maybe I don’t have enough.  A side effect of levodopa is dyskinesia (bobbing and weaving), but that’s after years of taking the drug, not right away like this.  I’ve got an appointment with my (extremely patient) neurologist in a couple weeks.   In the meantime, I’m trying to increase the exercise routine.  Gotta go – the alarm rang and it’s time to take another levodopa.

Deep Dive into DBS

I have a couple Parkie friends who are contemplating DBS.   DBS stands for Deep Brain Stimulation, a brain surgery that is not a cure for Parkinson’s but ameliorates some of the symptoms for a while.  I’m far away from this therapy and  it may not even be appropriate for me, but I thought I’d find out a bit more.

What is Deep Brain Stimulation?
I know, this sounds like something mad scientists in the Deep State do to you.  The actual description doesn’t make you feel any warmer and fuzzier: someone (hopefully with a LOT of experience and VERY steady hands) implants electrodes in your brain sending continuous electrical signals to specific target areas of the brain, which block the impulses that cause neurological dysfunctions. You have a little pacemaker in your chest just like the cardiac version.  Oh, and just to fill you full of confidence, they really don’t know how this works.  The American Association of Neurological Surgeons’ (AANS) webpage says, “DBS is presumed to help modulate dysfunctional circuits…”  That “presumed” gives me some pause.

Is it true you’re awake during the brain surgery??? (Yikes!)
Yes, it just gets better, doesn’t it?  More from the AANS webpage: “A small opening is made in the skull under a local anesthetic. The patient is awake during the DBS surgery to allow the surgical team to assess his or her brain functions. While the lead (electrode) is being advanced through the brain, the patient does not feel pain because of the human brain’s unique inability to generate pain signals.” Gee, doesn’t make me feel calmer.   

What’s the history and track record of DBS?
Scary as the procedure sounds, DBS has been around for a long time.  As far back as the 1950s, it originally was used to treat intractable pain.  By the early 1990s, DBS was expanded to movement disorders such as essential tremor, Parkinson’s disease, dystonia and multiple sclerosis, with more than 35,000 DBS implants worldwide

 Who are appropriate candidates for DBS?
 DBS is usually done in people who have had Parkinson’s for at least four years and still get a benefit from medication but have motor complications, such as significant “off” time (periods when medication isn’t working well and symptoms return) and/or dyskinesia (uncontrolled, involuntary movements).   Dementia is, alas, an all too common symptom of Parkinson’s, and typically a deal-killer for DBS – you have to be lucid during the surgery, and DBS may make cognitive skills fuzzier. 

What are the expected positive outcomes of DBS?
 DBS typically works best to lessen motor symptoms like stiffness, slowness and tremor. It doesn’t work as well for imbalance, freezing when walking or non-motor symptoms.   A general rule is that DBS will likely improve Parkinson’s symptoms that respond to medication. (The opposite is also true: symptoms that don’t get better with medication probably won’t respond to DBS.) 

What are the side effects of DBS?
DBS may exacerbate thinking or memory problems.  Evaluation and education of the patient to determine whether to  the surgery is appropriate is a critical step, and may typically include detailed memory/thinking testing to detect any cognitive problems that could worsen after DBS. 

What happens after surgery?
You’re not done yet, nor do you get to throw out your drugs. A few weeks after surgery, a movement disorder specialist uses a handheld programmer to set parameters, tailored to each individual’s unique symptoms, into the neurostimulator. (That’s the brain “pacemaker”.)  The DBS settings are gradually tweaked over time and medications are simultaneously adjusted. Most people are able to decrease (but not completely discontinue) Parkinson’s drugs after DBS. Determining the optimal combination of drugs and DBS settings — that which gives the most benefit and the least side effects — can take several months and even up to a year.

How long does DBS last?
DBS is not a cure for Parkinson’s, only a relief of some symptoms.  So the disease keeps progressing (or as I like to think of it, regressing).  Andres Lozano, MD, PhD, a DBS pioneer, was one of the authors of a study following up on patients who had had DBS 10  years previously.  He reported, “We found that the motor symptoms associated with PD — tremor, rigidity, and bradykinesia, or slowness of movement — were improved after the procedure. Moreover, the benefit to these symptoms was sustained up to ten years. However, we found that in some aspects, in particular posture and gait, the patients were worse. Non-motor symptoms, such as cognitive impairment, fatigue and digestion issues, unfortunately also continued along their natural course without much influence from the surgery. ”

Does my insurance cover DBS?
For my American readers, this is the critical question.  I found this reassuring response on a medical site by the University of Michigan: “DBS is FDA-approved and covered by most health insurance companies. Some insurance companies require prior authorization before having surgery, and some do not fully understand DBS and may initially deny coverage. However, usually with some detailed explanation, the decision is reversed. Denial may be based on the false assumption that DBS is experimental.”

YouTube extra:  Andrew Johnson, whom I had the pleasure of meeting at the Montreal World Parkinson’s Congress in 2013, filmed himself with and without his DBS pacemaker turned on.  Quite dramatic (and scary).

What is the “new normal”?

Here in Seattle, we are anxiously awaiting tomorrow’s cooler temperatures, and offshore winds to blow away the gritty smoke from hundreds of wildfires all around us —  Washington, Oregon, northern California, British Columbia, and Alberta.   We have even had ash fall on our vehicles, and, quite disturbingly, we had the same gritty wildfires experience last year.  So we wonder if this is the “new normal”.

And I wonder if painful, slow hiking is the “new normal” for me.  I have been battling a stooped-over, curved posture for over a year now.   You’ll notice even in this posed picture, I am curving to one side.  This unnatural stance not surprisingly causes muscle pain in my lower back.  The pain gets worse when I am hiking uphill with a daypack, even though the pack is quite light.

Paul and I just came back from a camping trip in the Canadian Rockies.  Despite the smoke, we did many beautiful hikes, such as the lake near Lake Louise in this photo.  But by the end of the trip, I was in a lot of pain, and could barely drag myself along the trail – even fairly flat ones.

I have been babying myself since my return and feel much better now.   A professional massage helped a lot.   I’ve thought about things I can do differently on the next trip, which will also involve a lot of hiking.   First and foremost,  I need to do as many of my standard suite of stretching and strengthening exercises as I can.   This sounds like a no-brainer, but I dropped most of the exercises due to time and the logistical challenges of doing them while traveling in a camper.  Second, I need to be conscious of taking breaks, both during the day and during the trip, not doing strenuous (for me) hikes every day as I did on this trip.  Third, I need to not be shy about routinely popping a double dose of sodium naproxen (Alleve).  It helps, so I shouldn’t hesitate to use it.

When I get back from this next trip, I’ll investigate a posture brace.  And I’ve already moved up my next neurologist date to review my medications.  I have gone through several combinations this year, and still don’t feel like I have the right mix.  But I do feel better having an action plan – “new normal”? bah humbug!

Vocabulary lesson:  I have Camptocormia! This is “an extreme flexion of the toracolumbar spine that exacerbates by walking and is relieved in the supine position.” (In other words, I’m hunched over.)  Why are Parkies frequently hunched over?  Because we have Proprioceptive Dysfunction — this is a problem with perceiving your sense of the relative position of one’s own parts of the body and strength of effort being employed in movement.  I am sort of aware I’m leaning over, and sort of not.

YouTube extra:  Canada has a so much better national anthem than we Yanks do.  Here is a lovely recording by a women’s chorus out of Vancouver.  Not only do I like the quality of their singing and their diversity, they also have cool jewelry and outfits !

 

 

Team Players

Girls and young women pounding down the soccer field, deftly stopping the ball and then dribbling the ball towards the goal.  This is not an unusual sight – go to any city park or playfield during the school year and chances are likely you will find a soccer game in progress.  What is surprising is when you look more closely and realize the players’s braids and pony tails are flecked with….silver.

I just spent a remarkable weekend watching an adult women’s soccer team play several games in a national adult soccer tournament.  They were in the Over 60 age bracket, and are gleefully awaiting just a few more team members to age up so they can be on the young edge of the Over 65 age bracket.    (And yes, there is such a thing as Over 70 teams.)   I asked the goalie how old she was, and she proudly said, “66” only to have her teammate one up her by saying, “Well, I’m 68!”

Many have played together since the team was organized in 2005, but typically their zest for team athletics goes back much further.  I found this astounding given that these women all came of age before Title IX.  Title IX, passed in 1972 during the Nixon Administration, helped prevent gender discrimination in US educational athletic programs.  Back in the day, at my 2000-student high school, girls had only one team – tennis.

Although nearly everyone on the team sported knee braces, and although they all seemed suspiciously familiar with hip and knee surgery,  I found it inspiring to watch these women on the field.  This is the fourth time this East Coast team has played at this West Coast venue, and the fourth time they have made it all the way to the finals.  The slogan of these kick-butt ladies?  “CRUSH IT!”