Category Archives: Hope

A Good Life With Parkinson’s

“I choose to make the rest of my life the best of my life.” Louise Hay

“Avoiding problems you need to face is avoiding the life you need to live.” Paulo Coelho

Try to live following the advice of the opening quotes: Today renews your lease on the rest of your life, enjoy it (get up, get out, get going). Today acknowledge your Parkinson’s; give it a nudge, because you are ready for the battle and for life.

18.01.13b.Live_Better_PD

Live a better and healthier life by following this circle of words [yes, they all begin with the letter ‘F’ (click here to download the schematic above)]:
Fit/fitness-
Exercise as much as your body can take, then do some more. Getting/staying fit really matters in your battle with Parkinson’s.

Fortitude-
Stay strong in your effort with your adversity.

Food- Feed your brain properly, fuel your body well; it will make a difference.

Flexible (two definitions)-
Stay flexible by frequent (I mean really often) stretching; you’ve got a life-altering disorder, stay flexible and let your life follow what happens because it’ll be okay.

Fulltime– It takes time and effort to manage your life. You can find the time because managing your life well from this minute on will matter later in your life;

Faith (multiple definitions)– Believe in your ability to successfully navigate your life; trust in your loved ones to support your journey; believe that a higher entity truly loves you and acknowledges your strength and passion for life.

Forty-winks and sleep some more- The brain is like a sponge that fills up all day with fluid; sleep allows the brain to drain, to renew, to fire-up strong upon waking; sleep is a very good thing.

A Good Life With Parkinson’s: Our Common Bond and Hope
I feel your stiffness; I know it well.

I sense your troubled thoughts; my mind also has questions.
I notice your tremor; mine can act up too.
I perceive your frustation; life with Parkinson’s can be problematic.
I see your shuffle; my right leg drags when I’m tired.
I admire your strength; I’ve got it too.
I acknowledge your life-accomplishments; we are still the same person as before Parkinson’s.
I see your honor; our work our living makes a difference.
I see your smile; those around us still care for us, no matter what.
I feel your effort; like you, I’ll never give up.

“Life is an opportunity, benefit from it. Life is beauty, admire it. Life is a dream, realize it. Life is a challenge, meet it. Life is a duty, complete it. Life is a game, play it. Life is a promise, fulfill it. Life is sorrow, overcome it. Life is a song, sing it. Life is a struggle, accept it. Life is a tragedy, confront it. Life is an adventure, dare it. Life is luck, make it. Life is too precious, do not destroy it. Life is life, fight for it.” Mother Teresa

Cover photo credit: http://ognature.com/path-snow-winter-mist-sunset-sun-trees-wallpaper-iphone-6/

 

64 Quotes on Persistence to Help Your Journey With Parkinson’s Disease

“Kites rise highest against the wind – not with it!” Winston Churchill

“Energy and persistence conquer all things.” Benjamin Franklin

Introduction: On January 1, LinkedIn announced that I had a work anniversary of 32 years at The University North Carolina at Chapel Hill ( if you include my postdoc at UNC-CH, this is a grand total of 36 years). My dear friend Lisa Cox (she is a graduate of The University North Carolina at Chapel Hill) wrote to congratulate me and said the following: “Grateful for your commitment to the University and to your students. Your steadfast determination is to be commended.”  Her use of the words ‘steadfast determination’  got me thinking about the word persistent  (steadfast is a synonym for persistent) and this thinking led to the current blog post.

Persistence in the backdrop of staying hopeful:  I truly admire and enjoy reading works by Dr. Brené Brown. Her insight, research/writing and her thoughtful commentary on many different topics are truly remarkable.  She has studied hope when you have Parkinson’s hope is a very important word to embrace.  One of her stories on hope, mixed with persistence, deals with the work of C. R. Snyder, at the University of Kansas, Lawrence.  Embracing and expanding upon this work, “hope is a thought process; hope happens when (1) We have the ability to set realistic goals (I know where I want to go); (2) We are able to figure out how to achieve those goals, including the ability to stay flexible and develop alternative routes (I know how to get there, I’m persistent, and I can tolerate disappointment and try again); and (3) We believe in ourselves (I can do this!).” To read in-depth this presentation entitled “Learning to Hope–Brené Brown”, click here. And again the word ‘persistent’ stood out while reading this document.

Persistence and Parkinson’s: Persistence (per·sist·ence /pərˈsistəns/ noun) is defined as (1) firm or obstinate continuance in a course of action in spite of difficulty or opposition, and (2) the continued or prolonged existence of something.  If you’re going to thrive in the presence of Parkinson’s, you will definitely need persistence because you will be locked in a lifelong battle to resist its presence every minute of every day.  Besides being hopeful and positive, having persistence will help enable your daily journey with Parkinson’s.  In other words, persistence is not giving up without trying,  searching out and exploring new pathways for your life, and it certainly demands steadfast determination.

64* Quotes on Persistence to Help You Stay Positive and Hopeful, and to Keep You Exercising: (*Why 64? Because I’m 64 years old) I started with >100 quotes and ended up with this list; they are arranged alphabetically by the author’s first name. [This is the third time I’ve written about persistence in the presence of Parkinson’s; to read the first blog post “Persistence and Parkinson’s” click here, and to read the most recent blog post “Chapter 7: A Parkinson’s Reading Companion on Persistenceclick here.]  May these quotes about persistence bolster your daily dealing with this dastardly disorder named Parkinson’s.

  1. “I do the very best I know how, the very best I can and I mean to keep doing so until the end.” Abraham Lincoln
  2. “It’s not that I’m so smart, it’s just that I stay with problems longer.” Albert Einstein
  3. “The best view comes after the hardest climb.” Anonymous/Unknown
  4.  “Strength does not come from winning. Your struggles develop your strengths. When you go through hardships and decide n.ot to surrender, that is strength.” Arnold Schwarzenegger
  5. “We are what we repeatedly do. Excellence, then, is not an act, but a habit.” Aristotle
  6. “Things turn out best for the people who make the best out of the way things turn out.” Art Linkletter
  7. “Better is possible. It does not take genius. It takes diligence. It takes moral clarity. It takes ingenuity. And above all, it takes a willingness to try.” Atul Gawande
  8. “You just can’t beat the person who never gives up.” Babe Ruth
  9. “History has demonstrated that the most notable winners usually encountered heartbreaking obstacles before they triumphed. They won because they refused to become discouraged by their defeat.” C. Forbes
  10. “As long as there’s breath in You–Persist!” Bernard Kelvin Clive
  11. “No great achievement is possible without persistent work.” Bertrand Russell
  12. “My greatest point is my persistence. I never give up in a match. However down I am, I fight until the last ball. My list of matches shows that I have turned a great many so-called irretrievable defeats into victories.” Bjorn Borg
  13. “In the confrontation between the stream and the rock, the stream always wins – not through strength, but through persistence.” Buddha
  14. “Nothing in the world can take the place of persistence. Talent will not; nothing is more common than unsuccessful men with talent. Genius will not; unrewarded genius is almost a proverb. Education will not; the world is full of educated derelicts. Persistence and determination alone are omnipotent.” Calvin Coolidge
  15. “Success is the result of perfection, hard work, learning from failure, loyalty, and persistence.” Colin Powell
  16. “It does not matter how slowly you go as long as you do not stop.” Confucius
  17.  “Don’t let the fear of the time it will take to accomplish something stand in the way of your doing it. The time will pass anyway; we might just as well put that passing time to the best possible use.” Earl Nightingale
  18. “A little more persistence, a little more effort, and what seemed hopeless failure may turn to glorious success.”Elbert Hubbard
  19. “If you are doing all you can to the fullest of your ability as well as you can, there is nothing else that is asked of a soul.” Gary Zukav
  20. ”Morale is the state of mind. It is steadfastness and courage and hope. It is confidence and zeal and loyalty. It is elan, esprit de corps and determination.” George C. Marshall
  21. “You go on. You set one foot in front of the other, and if a thin voice cries out, somewhere behind you, you pretend not to hear, and keep going.” Geraldine Brooks
  22. “Knowing trees, I understand the meaning of patience. Knowing grass, I can appreciate persistence.” Hal Borland
  23. “Perseverance is a great element of success. If you only knock long enough and loud enough at the gate, you are sure to wake up somebody.” Henry Wadsworth Longfellow
  24. “The difference between perseverance and obstinacy is, that one often comes from a strong will, and the other from a strong won’t.” Henry Ward Beecher
  25. “When you have a great and difficult task, something perhaps almost impossible, if you only work a little at a time, every day a little, suddenly the work will finish itself.” Isak Dinesen
  26. “Look at a stone cutter hammering away at his rock, perhaps a hundred times without as much as a crack showing in it. Yet at the hundred-and-first blow it will split in two, and I know it was not the last blow that did it, but all that had gone before.” Jacob A. Riis
  27. “The most essential factor is persistence–the determination never to allow your energy or enthusiasm to be dampened by the discouragement that must inevitably come.” James Whitcomb Riley
  28. ”We all have dreams. But in order to make dreams come into reality, it takes an awful lot of determination, dedication, self-discipline, and effort.” Jesse Owens
  29. “This is the highest wisdom that I own; freedom and life are earned by those alone who conquer them each day anew.” Johann Wolfgang von Goethe
  30. “Courage and perseverance have a magical talisman, before which difficulties disappear and obstacles vanish into air.” John Quincy Adams
  31. “Perseverance is failing 19 times and succeeding the 20th.” Julie Andrews
  32. “If you wish to be out front, then act as if you were behind.” Lao Tzu
  33. “You aren’t going to find anybody that’s going to be successful without making a sacrifice and without perseverance.“ Lou Holtz
  34. “Let me tell you the secret that has led me to my goal. My strength lies solely in my tenacity.” Louis Pasteur
  35. “Full effort is full victory.” Mahatma Gandhi
  36. “You’re not obligated to win. You’re obligated to keep trying to do the best you can every day.” Marina Wright Edelman
  37. “If you can’t fly, then run, if you can’t run then walk, if you can’t walk then crawl, but whatever you do, you have to keep moving forward.” Martin Luther King, Jr.
  38. “Courage doesn’t always roar, sometimes it’s the quiet voice at the end of the day whispering I will try again tomorrow.” Mary Anne Radmacher
  39. “Courage is the most important of all the virtues because without courage, you can’t practice any other virtue consistently.” Maya Angelou
  40. “You may encounter many defeats, but you must not be defeated. In fact, it may be necessary to encounter the defeats, so you can know who you are, what you can rise from, how you can still come out of it.” Maya Angelou
  41. “I’ve missed more than 9,000 shots in my career. I’ve lost almost 300 games. 26 times, I’ve been trusted to take the game winning shot and missed. I’ve failed over and over and over again in my life. And that is why I succeed.” Michael Jordan
  42. “Give the world the best you have and you may get hurt. Give the world your best anyway.” Mother Theresa
  43. “Patience, persistence, and perspiration make an unbeatable combination for success.” Napoleon Hill
  44. “It always seems impossible until it is done.” Nelson Mandela
  45. “I will persist until I succeed. Always will I take another step. If that is of no avail I will take another, and yet another. In truth, one step at a time is not too difficult. I know that small attempts, repeated, will complete any undertaking.” Og Mandino
  46. “Enter every activity without giving mental recognition to the possibility of defeat. Concentrate on your strengths, instead of your weaknesses… on your powers, instead of your problems.” Paul J. Meyer
  47. “He conquers who endures.” Persius
  48. “Our greatest glory is not in never failing, but in rising up every time we fail.” Ralph Waldo Emerson
  49. “We are human. We are not perfect. We are alive. We try things. We make mistakes. We stumble. We fall. We get hurt. We rise again. We try again. We keep learning. We keep growing. And we are thankful for this priceless opportunity called life.” Ritu Ghatourey
  50.  “Success is the sum of small efforts, repeated day in and day out.” Robert Collier
  51. “The best way out is always through.” Robert Frost
  52. “Your hardest times often lead to the greatest moments of your life. Keep going. Tough situations build strong people in the end.” Roy Bennett
  53. “There are two ways of attaining an important end, force and perseverance; the silent power of the latter grows irresistible with time.” Sophie Swetchine
  54. “To succeed, you must have tremendous perseverance, tremendous will. “I will drink the ocean,” says the persevering soul; “at my will mountains will crumble up.” Have that sort of energy, that sort of will; work hard, and you will reach the goal.” Swami Vivekananda
  55. “Our greatest weakness lies in giving up. The most certain way to succeed is to always try just one more time.” Thomas Edison
  56. “Permanence, perseverance, and persistence in spite of all obstacles, discouragement, and impossibilities: It is this, that in all things distinguishes the strong soul from the weak.” Thomas Carlyle
  57. “With ordinary talent and extraordinary perseverance, all things are attainable.” Thomas Foxwell Buxton
  58. “I’m a great believer in luck, and I find the harder I work, the more I have of it.” Thomas Jefferson
  59. “We are made to persist. That’s how we find out who we are.” Tobias Wolff
  60. “I am not judged by the number of times I fail, but by the number of times I succeed: and the number of times I succeed is in direct proportion to the number of times I fail and keep trying.” Tom Hopkins
  61. “The quality of a person’s life is in direct proportion to their commitment to excellence regardless of their chosen field of endeavor.”  Vince Lombardi
  62. “Most people never run far enough on their first wind to find out they’ve got a second.” William James
  63. “Continuous effort–not strength or intelligence–is the key to unlocking our potential.” Winston Churchill
  64. “If you’re going through hell, keep going. Winston Churchill
Motivation using quotes on persistence and pictures/diagrams/ideas related to Parkinson’s:  I am a very visual person and I also need motivation as the new year begins with winter cold in North Carolina  (yes, we got some snow/freezing rain/ice, and yes Chapel Hill was mostly brought to a standstill; so we move on and hope for an early spring).  Therefore, to help me stay motivated to exercise every day,  and to remind me of all the benefits that exercise provides me against Parkinson’s progression I made the following images.

 

 Also displayed below are 12 additional quotes mounted on some colorful artful backgrounds.   Hopefully, this will provide you a template to make your own favorite motivational group of persistence quotes.

Please stay focused on taking the best care of you by working well with your family and support team, be honest with your movement disorder Neurologist, get plenty of exercise and try to sleep well.  You hold the key to unlock the plan to manage your Parkinson’s.

“Strength is found in each of us.  For those of us with Parkinson’s, we use our personal strengths of character to bolster our hope, courage, mindfulness/contentment/gratitude, determination, and the will to survive. Stay strong. Stay hopeful. Stay educated. Stay determined. Stay persistent. Stay courageous. Stay positive. Stay wholehearted. Stay mindful. Stay happy. Stay you.”  Frank C. Church

Cover Photo credit: http://www.wallpaperup.com/202084/morning_ice_sunrise_lake_snow_forest_winter_reflection.html

Complementary and Alternative Medicine (CAM) and Over-the-Counter Therapies in Parkinson’s

With Parkinson’s, exercise is better than taking a bottle of pills. If you don’t do anything you’ll just stagnate.” Brian Lambert

“With Parkinson’s you have two choices: You can let it control you, or you can control it. And I’ve chosen to control it.” US Senator Isakson

Introduction: Having one of the numerous neurodegenerative disorders can be disheartening, difficult and life-threatening/ending; however, Parkinson’s remains in the forefront of treatment schemes and therapeutic options.  We may have a slowly evolving disorder, yet I remain firmly entrenched both in striking back to try-to-slow its progression and in remaining hopeful that new advances are on the horizon to throttle-back its progression.  Recently, several people have asked for an update on my strategy for treating Parkinson’s.  My plan consists of (i) traditional Parkinson’s medication,  (ii) supplemented by a complementary and alternative medicine (CAM) approach, and (iii) fueled by exercise. My philosophy is simple because I truly believe there are steps I can follow to remain as healthy as possible, which include having a positive mindset to support this effort, and to accept the axiom of the harder I try the better I’ll be.

“Life is to be lived even if we are not healthy.” David Blatt

Complementary and Alternative Medicine (CAM):The National Institutes of Health defines CAM as follows: “Complementary and alternative medicine (CAM) is the term for medical products and practices that are not part of standard medical care. ‘Complementary medicine’ refers to treatments that are used with standard treatment. ‘Alternative medicine’ refers to treatments that are used instead of standard treatment.”  Here is a nice overview of CAM (click here). The National Center for CAM (click here for NCCAM) gives five categories to broadly describe CAM (see below, and followed by some representative components for each of the 5 categories):

17.12.31.CAM_Summary

(1) Alternative medical systems include treatment by traditional Chinese medicine, Ayurveda and naturopathic medicine;
(2) Mind-body interventions like mindfulness meditation;
(3) Biologically-based therapies include over-the-counter natural products and herbal therapies;
(4) Manipulative and body-based methods describe chiropractic and massage therapies;
(5) Energy therapies include techniques such as Reiki and therapeutic touch.

“My way of dealing with Parkinson’s is to keep myself busy and ensure my mind is always occupied.” David Riley

CAM and Parkinson’s: Published CAM clinical trial studies have yielded only a sliver of positive response to slowing the progression of Parkinson’s, several were halted due to no change compared to the placebo-control group. Regardless of these ‘failed’ studies, many have embraced a CAM-based approach to managing their disorder, including me. Please remember that I’m not a clinician, and I’m not trying to convince you to adopt my strategy.  I am a biochemist trained in Hematology but I do read and ponder a lot, especially about Parkinson’s.  We know a lot about Parkinson’s and we’re learning a lot about the molecular details to how it promotes the disease.  There is not a cure although we have a growing array of drugs for therapeutic intervention.  Without a  cure, we look at the causes of Parkinson’s (see schematic below), we consider various CAM options, and we go from there (see schematic below). If you venture into adding to your portfolio of therapy, it is imperative you consult with your Neurologist/family medicine physician beforehand.  Your combined new knowledge with their experience can team-up to make an informed decision about your herb, over-the-counter compound use and its potential benefit/risk ratio.

17.12.31.PD_Cause.CAM“I discovered that I was part of a Parkinson’s community with similar experiences and similar questions that I’d been dealing with alone.”Michael J. Fox

A strategy for treating Parkinson’s: The treatment plan I follow uses traditional medical therapy, CAM (several mind-body/manual practices and numerous natural products) and the glue that ties it all together is exercise.  Presented here is an overview of my medical therapy and CAM natural products. I only list the exercises I am using, not describe or defend them.  Due to my own personal preference for the length of a blog post, I will return to them later this year and include an update of the mind-body/manual practices that I’m currently using. Please note that these views and opinions expressed here are my own. Content presented here is not meant as medical advice. Definitely consult with your physician before taking any type of supplements.   The schematic below gives a ‘big-picture’ view of my treatment strategy.

18.01.01.Daily_Take. brain.druge.CAM.Exercise

To some, my treatment plan may seem relatively conservative. It has been developed through conversations with my Neurologist and Internist.  This was followed by studying the medical literature on what has worked in Parkinson’s treatment, the list of compounds to consider was defined/refined (actually, my choice of OTC compounds has been trimmed from several years ago).  My CAM drug/vitamin/natural products strategy for treating Parkinson’s goes as follows: a) compounds (reportedly) able to penetrate the blood brain barrier; b) compounds (possibly) able to slow progression of the disorder; c) compounds that either are anti-oxidative or are anti-inflammatory; d) compounds that don’t adversely alter existing dopamine synthesis/activity; e) compounds that support overall body well-being; and f) compounds that support specific brain/nervous system health/nutrition. [Please consult with your physician before taking any type of supplements.] The Table below presents a detailed overview of my strategy for treating Parkinson’s.

18.01.01.DailyTherapy4Note of caution: Most herbs and supplements have not been rigorously studied as safe and effective treatments for PD. The U.S. Food and Drug Administration (FDA) does not strictly regulate herbs and supplements; therefore, there is no guarantee of safety, strength or purity of supplements.

REPLACING DOPAMINE:
On a daily basis, I use a combination of Carbidopa/Levodopa (25 mg/100 mg tablet x 4 daily, every 5 h on an empty stomach if possible, typically 6AM, 11AM, 4PM, 9PM) and a dopamine agonist Requip XL [Ropinirole 6 mg total (3 x 2 mg tablets) x 3 daily, every 6 h, typically 6AM, noon, 6PM).  This treatment strategy and amount combining Carbidopa/Levodopa and Ropinirole has been in place for the past 18 months (NOTE: I stopped using the additional dopamine agonist Neupro transdermal patch Rotigotine). For an overview on Carbidopa/Levodopa, I highly recommend the following 2 papers:
[1.] Ahlskog JE. Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease. Mayo Clinic Proceedings. 2011;86(12):1211-6. doi: https://doi.org/10.4065/mcp.2011.0443.
[2.] 1. Espay AJ, Lang AE. Common Myths in the Use of Levodopa in Parkinson Disease: When Clinical Trials Misinform Clinical Practice. JAMA Neurol. 2017. doi: 10.1001/jamaneurol.2017.0348. PubMed PMID: 28459962.

ISRADIPINE:
An FDA-approved calcium-channel blocker (CCB) named Isradipine penetrates the blood brain barrier to block calcium channels and potentially preserve dopamine-making cells. Isradipine may slow the progression of Parkinson’s. The primary use of Isradipine is in hypertension; thus, to treat my pre-hypertension I switched from the diuretic Hydrochlorothiazide to the CCB Isradipine.  A CCB is a more potent drug than a diuretic; importantly, my blood pressure is quite normal now and maybe I’m slowing the progression of my Parkinson’s. Please see this blog post for a review of Isradipine (click here). [Please consult with your physician before taking any type of new medication.

ANTIOXIDANTS/VITAMINS/GENERAL HEALTH:
N-Acetyl-Cysteine (NAC; 600 mg x 3 daily) is a precursor to glutathione, a powerful anti-oxidant. In several studies, NAC has been shown to be neuroprotective in Parkinson’s (click here).  I have recently posted an overview of NAC (click here). Furthermore, the ‘Science of Parkinson’s disease’ has presented their usual outstanding quality in a blog post on NAC in PD (click here);
trans-Resveratrol (200 mg daily) is an antioxidant that crosses the blood-brain barrier, which could reduce both free-radical damage and inflammation in Parkinson’s. If you decide to purchase this compound, the biologically-active form is trans-Resveratrol. The ‘Science of Parkinson’s disease’ has an excellent blog post on Resveratrol in PD (click here);
Grape Seed (100 mg polyphenols, daily) is an antioxidant that crosses the blood-brain barrier, which could reduce both free-radical damage and inflammation in Parkinson’s;
Milk Thistle (Silybum Marianum, 300 mg daily) and its active substance Silymarin protects the liver.  Dr. Jay Lombard in his book, The Brain Wellness Plan, recommends people with PD who take anti-Parkinson’s drugs (metabolized through the liver) to add 300 mg of Silymarin (standardized milk thistle extract) to their daily medication regime.
Melatonin (3 mg 1 hr before sleep) Melatonin is a hormone that promotes sustained sleep. Melatonin is also thought to be neuroprotective (click here);
Probiotic Complex with Acidophilus is a source of ‘friendly’ bacteria to contribute to a healthy GI tract.
Vitamin (daily multiple)
A high-potency multivitamin with minerals to meet requirements of essential nutrients, see label for content [I only take 1 serving instead  of the suggested 2 gummies due to my concern about taking a large amount of Vitamin B6 as described in a recent blog (click here)]:
IMG_2059 copyVitamin D3 (5000 IU 3 times/week) is important for building strong bones. Now we also know that vitamin D3 is almost like ‘brain candy’ because it stimulates hundreds of brain genes, some of which are anti-inflammatory and some support nerve health (click here). Supplementation with vitamin D3 (1200 IU/day) for a year slowed the progression of a certain type of Parkinson’s (click here). Furthermore, augmentation with vitamin D3 was recently shown to slow cognitive issues in Parkinson’s (click here).

NO LONGER TAKE Coenzyme Q10 (CoQ10), Creatine and Vitamin E because they did not delay the progression of Parkinson’s or they were harmful.
NO LONGER TAKE a high potency Vitamin B Complex (see label below) due to my concern that a large excess vitamin B6 could be detrimental to Carbidopa/Levodopa (click here for blog post):
Screen Shot 2018-01-02 at 11.39.56 PM
List of several recent PubMed peer-reviewed CAM reviews (includes a more comprehensive overview of all areas of CAM in treating Parkinson’s):
Bega D, Zadikoff C. Complementary & alternative management of Parkinson’s disease: an evidence-based review of eastern influenced practices. J Mov Disord. 2014;7(2):57-66. doi: 10.14802/jmd.14009. PubMed PMID: 25360229; PMCID: PMC4213533.

Bega D, Gonzalez-Latapi P, Zadikoff C, Simuni T. A Review of the Clinical Evidence for Complementary and Alternative Therapies in Parkinson’s Disease. Current Treatment Options in Neurology. 2014;16(10):314. doi: 10.1007/s11940-014-0314-5.

Ghaffari BD, Kluger B. Mechanisms for alternative treatments in Parkinson’s disease: acupuncture, tai chi, and other treatments. Curr Neurol Neurosci Rep. 2014;14(6):451. doi: 10.1007/s11910-014-0451-y. PubMed PMID: 24760476.

Kim HJ, Jeon B, Chung SJ. Professional ethics in complementary and alternative medicines in management of Parkinson’s disease. J Parkinsons Dis. 2016;6(4):675-83. doi: 10.3233/JPD-160890. PubMed PMID: 27589539; PMCID: PMC5088405.

Kim TH, Cho KH, Jung WS, Lee MS. Herbal medicines for Parkinson’s disease: a systematic review of randomized controlled trials. PLoS One. 2012;7(5):e35695. doi: 10.1371/journal.pone.0035695. PubMed PMID: 22615738; PMCID: PMC3352906.

Wang Y, Xie CL, Wang WW, Lu L, Fu DL, Wang XT, Zheng GQ. Epidemiology of complementary and alternative medicine use in patients with Parkinson’s disease. J Clin Neurosci. 2013;20(8):1062-7. doi: 10.1016/j.jocn.2012.10.022. PubMed PMID: 23815871. 

Today we take control over our Parkinson’s:
Please stay focused on dealing with your disorder.
Please learn as much as you can about Parkinson’s.
Please work with your neurologist to devise your own treatment strategy.
Please stretch and exercise on a daily basis, it will make a difference.
Please be involved in your own disorder; it matters that you are proactive for you.
Please stay positive and focused as you deal with this slowly evolving disease.
Please stay hopeful you can mount a challenge to slow the progression.
Please remain persistent; every morning your battle renews and you must be prepared.

 

In the midst of winter, I found there was, within me, an invincible summer.  And that makes me happy. For it says that no matter how hard the world pushes against me, within me, there’s something stronger – something better, pushing right back.” Albert Camus

Cover photo credit: news.nowmedia.co.za/medialibrary/Article/109153/Wine-grape-crop-6-7-down-in-2016-800×400.jpg

 

Effect of Forgiveness on Health

“When you forgive, you in no way change the past – but you sure do change the future.”  Bernard Meltzer

“The first step in forgiveness is the willingness to forgive.” Marianne Williamson

Précis: Recently had a friend go through a difficult break-up from a marriage. The notion of getting past the failed relationship, achieving forgiveness, and moving on without causing illness was of paramount importance. The implications of forgiveness/unforgiveness as it relates to health-illness crossed my mind. It started with assembling the quotes in this post. Next, I did a Google Scholar search for “forgiveness and health” and discovered a whole new area of psychology-science-medicine (well, it was new to me). Most of us would agree that forgiving yourself promotes wellness; whereas remaining unforgiven could disrupt your mental and possibly even your physical health.  This post reviews forgiveness and its positive impact on our health.

“Forgiveness is really a gift to yourself – have the compassion to forgive others, and the courage to forgive yourself.” Mary Anne Radmach

Forgiveness and Health: The Oxford dictionary defines ‘forgive’ as to stop feeling angry and resentful towards (someone) for an offense, flaw, or mistake.  Positive psychology is the scientific study of the strengths that enable individuals and communities to thrive. Forgiveness is a big part of positive psychology regarding both physical and mental well-being.   Over the past 15 years, researchers have focused on 2 primary hypotheses: (1) forgiveness has important connections to physical health; and (2) this relationship is guided by an association between lack of forgiveness and anger.  Evidently, there is consensus in the field that these two primary processes form the basis of forgiveness: (i) letting go of one’s right to resentment and negative judgment; and (ii) fostering undeserved compassion and generosity toward the perpetrator.  The first process implies a person would reduce their negative emotions (i.e., anger and revenge); while  the second process involves increasing positive feelings and might even include reconciliation. Collectively, there is growing scientific evidence that links the positivity of forgiveness and health.

“He who is devoid of the power to forgive is devoid of the power to love.” Martin Luther King, Jr.

“The more you know yourself, the more you forgive yourself.” Confucius

Forgiveness vs. Unforgiveness: It is probably apparent (to you) that forgiveness is generally associated with improved mental and physical health, as opposed to someone unable/unwilling to forgive.  Modeling the relationship between forgiveness and health, based on the hypothesis that forgiveness reduces hostility (and this would be considered healthier), 6 paths linking forgiveness and health have been described: (i) decrease in chronic blaming and anger; (ii) reduction in chronic hyper-arousal [“a state of increased psychological and physiological tension marked by such effects as reduced pain tolerance, anxiety, exaggeration of startle responses, insomnia, fatigue and accentuation of personality traits.”]; (iii) optimistic thinking; (iv) self-efficacy to take health-related actions; (v) social support; and (vi) transcendent consciousness (“state achieved through the practice of transcendental meditation in which the individual’s mind transcends all mental activity to experience the simplest form of awareness“).

What does this mean? The majority of studies on forgiveness indicate a reciprocal relationship to hostility, anger, anxiety and depression.  Forgiveness may directly alter sympathetic reactivity, which is often referred to as the “fight-or-flight” response. These responses include increases in heart rate, blood pressure, cardiac contractility, and cortisol.  This implies that unforgiveness could promote an acute, stress-induced reactivity that could be associated with general health problems.  However, it is much more complicated than this simplistic flow of events: anger is a component of unforgiveness; anger is a health risk; therefore, unforgiveness is a health risk.  This is really interesting reading but way beyond my training as a protein biochemist (If interested, look over the references listed below)

Forgiveness and Mental Health: Let’s take a different angle by looking at mental health. We begin with unforgiveness as being associated with stress from an ‘interpersonal’ offense and stress is associated with diminished mental health. Furthermore, unforgiveness due to an ‘intrapersonal’ wrongdoing may lead to shame, regret and guilt, which could also negatively affect mental health. The positive impact of forgiveness may help correct the downturn in mental health that resulted from either interpersonal or intrapersonal stress.  In many instances, mental health is linked to physical health. This suggests that practicing forgiveness would positively influence mental health and could therein bolster physical health.

To summarize the ability of forgiveness to bolster mental health, I have re-drawn the figure from Toussaint and Webb  (2005) as a 4-piece puzzle. It begins with the ‘direct effect’ of forgiveness as told through unforgiveness with emotions of resentment, bitterness, hatred, residual hostility, and fear. The negative emotions of unforgiveness could contribute significantly to mental health problems.  By contrast, the emotion of forgiveness is positive and strong and love-based that could improve mental health. The ‘indirect effect’ of forgiveness through social support, interpersonal behavior and health behavior are all positively-linked to good mental health. The ‘developmental stage’ describes the recognition of the problem, need for an alternative solution, and ultimately the effect of forgiveness augments mental health.  The final piece to the puzzle is the ‘attributional process’, which suggests that being able to forgive bolsters personal control of one’s life, which is perceived to be positive.  By contrast, unforgiveness blocks this life-controlling process by consumptive negative emotions made worse in the individual through rumination.  Due to my own internal word limit and time-period to read/understand the topic, I have not included the religious or spiritual basis of the forgiveness of God, feeling God’s forgiveness, and seeking God’s forgiveness in the narrative of this post.  For many people, these would be integral components to the discussion here on forgiveness and its overall impact on both mental and physical health.

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“I don’t know if I continue, even today, always liking myself. But what I learned to do many years ago was to forgive myself. It is very important for every human being to forgive herself or himself because if you live, you will make mistakes- it is inevitable. But once you do and you see the mistake, then you forgive yourself and say, ‘Well, if I’d known better I’d have done better,’ that’s all.” Maya Angelou

9 Steps to Forgiveness (Fred Luskin, LearningToForgive.com): Dr. Luskin is a noted-researcher in the field of forgiveness. His belief is that by practicing forgiveness, your anger, hurt, depression and stress will all be reduced and it will increase feelings of hope, compassion and self confidence. Furthermore, he believes that practicing forgiveness contributes to healthy relationships and to improved physical health; here are the 9 steps to forgiveness:

  1. Know exactly how you feel about what happened and be able to articulate what about the situation is not OK. Then, tell a trusted couple of people about your experience.
  2. Make a commitment to yourself to do what you have to do to feel better. Forgiveness is for you and not for anyone else.
  3. Forgiveness does not necessarily mean reconciliation with the person that hurt you, or condoning of their action. What you are after is to find peace. Forgiveness can be defined as the “peace and understanding that come from blaming that which has hurt you less, taking the life experience less personally, and changing your grievance story.”
  4. Get the right perspective on what is happening. Recognize that your primary distress is coming from the hurt feelings, thoughts and physical upset you are suffering now, not what offended you or hurt you two minutes – or ten years – ago. Forgiveness helps to heal those hurt feelings.
  5. At the moment you feel upset practice a simple stress management technique to soothe your body’s flight or fight response.
  6. Give up expecting things from other people, or your life, that they do not choose to give you. Recognize the “unenforceable rules” you have for your health or how you or other people must behave. Remind yourself that you can hope for health, love, peace and prosperity and work hard to get them.
  7. Put your energy into looking for another way to get your positive goals met than through the experience that has hurt you. Instead of mentally replaying your hurt seek out new ways to get what you want.
  8. Remember that a life well lived is your best revenge. Instead of focusing on your wounded feelings, and thereby giving the person who caused you pain power over you, learn to look for the love, beauty and kindness around you. Forgiveness is about personal power.
  9. Amend your grievance story to remind you of the heroic choice to forgive.

“Forgiving does not erase the bitter past. A healed memory is not a deleted memory. Instead, forgiving what we cannot forget creates a new way to remember. We change the memory of our past into a hope for our future.” Lewis B. Smedes

Forgiveness in the Presence of Parkinson’s:  Receiving a diagnosis of Parkinson’s, a lifelong chronic progressive neurodegenerative disorder is a real shock.  The diagnosis comes with a variety of emotions. After a while, acceptance takes over; no, not your identify, just ok, I’ve got Parkinson’s, live through it, make the most of this experience. Eventually I had to put forgiveness into part of this living-life-equation. There were two self-involved events where I might have contributed to the development of my own disease.  The first was as a young boy in the summertime riding my bicycle behind the DDT trucks spraying for mosquitoes on our Air Force bases [Dichlorodiphenyltrichloroethane (DDT) is a colorless, tasteless, and almost odorless crystalline organochlorine known for its insecticidal properties]. DDT is one of the known chemical inducers of Parkinson’s. Second, in graduate school before OSHA took over regulating lab safety, I routinely used many different noxious compounds for the benefit of science and for the completion of my PhD. Both events caused me to pause and ponder; however, I decided to forgive myself. I truly believe had I remained unforgiving, I would have paved a path of ill health.

This whole process of dealing with the emotion from diagnosis to acceptance (and forgiveness) of Parkinson’s reminds me of the opening verse of “We Are The Champions” by Queen: “I paid my dues/ time after time./ I’ve done my sentence/ but committed no crime./ And bad mistakes-/ I’ve made a few./ I’ve had my share of sand kicked in my face/ but I’ve come through./  (And I need to go on and on, and on, and on)

The vast majority of people with Parkinson’s are 60-years of age or older (although there is a group of early-age-onset). Interestingly, in a recent study with an elderly population, forgiveness showed positive and significant association with mental and physical health.

“You cannot travel back in time to fix your mistakes, but you can learn from them and forgive yourself for not knowing better.” Leon Brown

“Accept the past as past, without denying it or discarding it.” Mitch Albom

Forgive Ourselves: Dr. Elaine in her post “The-healing-power-of-forgiveness” nicely summarized self-forgiveness: “We tend to believe that forgiveness supports the transgression that has been committed against us. But forgiveness is not an endorsement of wrongdoing; rather, it’s an act of releasing the pain and hurt it caused through love, the root of forgiveness—and it is not love of the other but of the self. We must forgive ourselves as well as others in order to be whole and healed.”

Effect of Forgiveness on Health: The sum total of our health is a complex formula that differs slightly for each one of us.  Those of us with a progressive neurodegenerative disorder like Parkinson’s increases the complexity of this life-equation.  Thus, dealing with the axis defined by forgiveness/unforgiveness in the matter of health (both mental and physical) clearly could complicate our health.  Truly we need to add forgiveness as a filter to our life-lens; the benefits from this addition should favor our health in the long-run.

“If we all hold on to the mistake, we can’t see our own glory in the mirror because we have the mistake between our faces and the mirror; we can’t see what we’re capable of being. You can ask forgiveness of others, but in the end the real forgiveness is in one’s own self.” Maya Angelou

Cover photo credit: https://orig05.deviantart.net/0a42/f/2015/095/1/6/painted_wallpaper___fog_on_lake_by_dasflon-d8oiudk

Useful References:

Lawler KA, Younger JW, Piferi RL, Jobe RL, Edmondson KA, Jones WH. The Unique Effects of Forgiveness on Health: An Exploration of Pathways. Journal of Behavioral Medicine. 2005;28(2):157-67. doi: 10.1007/s10865-005-3665-2.

Akhtar, S., Dolan, A., & Barlow, J. (2017). Understanding the Relationship Between State Forgiveness and Psychological Wellbeing: A Qualitative Study. Journal of Religion and Health, 56(2), 450–463. http://doi.org.libproxy.lib.unc.edu/10.1007/s10943-016-0188-9

Lawler-Row KA, Karremans JC, Scott C, Edlis-Matityahou M, Edwards L. Forgiveness, physiological reactivity and health: The role of anger. International Journal of Psychophysiology. 2008;68(1):51-8. doi: https://doi.org/10.1016/j.ijpsycho.2008.01.001.

Rey L, Extremera N. Forgiveness and health-related quality of life in older people: Adaptive cognitive emotion regulation strategies as mediators. Journal of Health Psychology. 2016;21(12):2944-54. doi: 10.1177/1359105315589393. PubMed PMID: 26113528.

Toussaint, L., J.R. Webb.  Theoretical and empirical connections between forgiveness, mental health, and well-being E.L. Worthington Jr (Ed.), Handbook of forgiveness, Brunner–Routledge, New York (2005), pp. 207-226

 

 

 

 

Parkinson’s Disease Research: A Commentary from the Stands and the Playing Field

“You can have a very bad end with Parkinson’s, but on the other hand, you can be like me, because I’m lucky. I’m not having a bad end.” Margo MacDonald

“My age makes me think how valuable life is. How bad is something like Parkinson’s in relation to not having life at all?” Michael J. Fox

Introduction: Last month, together with Dr. Simon Stott and his team of scientists (The Science of Parkinson’s Disease), we co-published a historical timeline of Parkinson’s disease beginning with the description of the ‘shaking palsy’ from James Parkinson in 1817. My post entitled “Milestones in Parkinson’s Disease Research and Discovery” can be read here (click this link). The Science of Parkinson’s Disease post entitled “Milestones in Parkinson’s Disease Research and Discovery” can be read here (click this link).

We spent a lot of time compiling and describing what we felt were some of the most substantial findings during the past 200 years regarding Parkinson’s disease.  I learned a lot; truly amazing what has been accomplished in our understanding of  such a complex and unique disorder.  Simon posted a follow-up note entitled “Editorial: Putting 200 years into context” (click this link). I have decided to also post a commentary from the standpoint of (i) being someone with Parkinson’s and (ii) being a research scientist.

“Every strike brings me closer to the next home run.” Babe Ruth

Baseball: I want to use the analogy of a baseball game to help organize my commentary. Baseball fans sit in the stands and have fun watching the game, thinking about the strategy behind the game, eating/drinking, and sharing the experience with family/friends/colleagues.   Most baseball players begin playing early in life and the ultimate achievement would be to reach the major leagues. And this would usually have taken many years of advancing through different levels of experience on the part of the ballplayer. How does how this analogy work for me in this blog? Stands: I am a person-with-Parkinson’s watching the progress to treat and/or cure this disorder. Playing field: I am a research scientist in a medical school (click here to view my training/credentials).

“Never allow the fear of striking out keep you from playing the game!”  Babe Ruth

Observation from the stands:
I am a spectator like everyone else with Parkinson’s. I read much of the literature available online.  Like you, I think about my disorder; I think about how it’s affecting me every day of my life. Yes, I want a cure for this disease.  Yes, I’m rather impatient too.  I understand the angst and anxiety out there with many of the people with Parkinson’s. In reality, I would not be writing this blog if I didn’t have Parkinson’s. Therefore, I truly sense your frustration that you feel in the presence of Parkinson’s, I do understand.  Given below are examples of various organizations and ads and billboards in support of finding a cure for Parkinson’s.  Some even suggest that a cure must come soon.   However, the rest of my post is going to be dedicated to trying to explain why it’s taking so long; why I am optimistic and positive a cure and better treatment options are going to happen.  And it is partly based on the fact that there really are some amazing people working to cure Parkinson’s and to advance our understanding of this disorder.

“When you come to a fork in the road take it.” Yogi Berra

Observations from the playing field (NIH, war on cancer, research lab, and advancing to a cure for Parkinson’s):

National Institutes of Health (NIH) and biomedical research in the USA: Part of what you have to understand, in the United States at least, is that a large portion of biomedical research is funded by the NIH (and other federally-dependent organizations), which receives a budget from Congress (and the taxpayers). What does it mean for someone with Parkinson’s compared to someone with cancer or diabetes? The amount of federal funds committed to the many diseases studied by NIH-funded-researchers are partly divvied up by the number of people affected. I have prepared a table from the NIH giving the amount of money over the past few years for the top four neurodegenerative disorders, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and Huntington’s Disease, respectively [taken from “Estimates of Funding for Various Research, Condition, and Disease Categories” (click here)]. And this is compared to cancer and coronary arterial disease and a few other major diseases. Without going into the private organizations that fund research, a large amount of money comes from the NIH. Unfortunately, from 2003-2015, the NIH lost >20% of its budget for funding research (due to budget cuts, sequestration, and inflationary losses; click here to read further).   Therefore,  it is not an overstatement to say getting  funded today by the NIH is fiercely competitive.  From 1986 to 2015, my lab group was supported by several NIH grants and fellowships  (and we also received funding from the American Heart Association and Komen for the Cure).

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“In theory, there is no difference between theory and practice. But in practice, there is.” Yogi Berra

War against cancer: In 1971, Pres. Richard Nixon declared war against cancer and Congress passed the National Cancer Act.  This created a new national mandate “to support research and application of the results of research to reduce the incident, morbidity, and mortality from cancer.” Today, cancer is still the second leading cause of death in the USA; however, we’ve come such a long way to improving this statistic from when the Cancer Act was initiated.

Scientifically, in the 1970’s, we were just learning about oncogenes and the whole field of molecular biology was really in its infancy. We had not even started sequencing the human genome, or even of any organism.  We discovered genes that could either promote or suppress cellular growth.   We began to delineate the whole system of cell signaling and communications with both normal and malignant cells. We now know there are certain risk factors that allow us to identify people that may have increased risk for certain cancers. Importantly,  we came to realize that not all cancers were alike,  and it offered the notion to design treatment strategies for each individual cancer.  For example,  we now have very high cure rates for childhood acute leukemia and Hodgkin’s lymphoma and we have significantly improved survival statistics for women with breast cancer. Many might say this was a boondoggle and that we wasted billions of dollars  funding basic biomedical research on cancer; however, basic  biomedical research is expensive and translating that into clinical applications is even more expensive.  [ For a  very nice short review on cancer research please see the following article, it may be freely accessible by now: DeVita Jr, Vincent T., and Steven A. Rosenberg. “Two hundred years of cancer research.” New England Journal of Medicine 366.23 (2012): 2207-2214.]

“One of the beautiful things about baseball is that every once in a while you come into a situation where you want to, and where you have to, reach down and prove something.” Nolan Ryan

The biomedical research laboratory environment:  A typical laboratory group setting is depicted in the drawing below. The research lab usually consists of the lead scientist who has the idea to study a research topic, getting grants funded and in recruiting a lab group to fulfill the goals of the project.  Depending on the philosophy of the project leader the lab may resemble very much like the schematic below or may be altered to have primarily technicians or senior postdoctoral fellows working in the lab  (as two alternative formats). A big part of academic research laboratories is education and training the students and postdocs to go on to advance their own careers; then you replace the people that have left and you continue your own research.  Since forming my own lab group in 1986, I have helped train over 100 scientists in the research laboratory: 17 graduate students, 12 postdoctoral fellows, 17 medical students, and 64 undergraduates. The lab has been as large as 10 people and a small as it is currently is now with two people. People come to your lab group because they like what you’re doing scientifically and this is where they want to belong for their own further training and advancement.  This description is for an academic research  laboratory; and  I should also emphasize that many people get trained in federal government-supported organizations, private Pharma and other types of research environments that may differ in their laboratory structure and organizational format.

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“Hitting is 50% above the shoulders.” Ted Williams

 In search of the cure for Parkinson’s:    First, I understand the situation you’re in with Parkinson’s because I’m living through the same situation.   But when people find out I’m a research scientist they always wonder why aren’t we doing more to find a cure, and I  hear the sighs of frustration and I see the anxiety in their faces. Second, the previous three sections are not meant to be an excuse for why there is still no cure for Parkinson’s. It is presented in the reality of what biomedical research scientists must undergo to study a topic.  Third, the experiments that take place in basic biomedical research laboratory may happen over weeks to months if successful. Taking that laboratory data to the clinic and further takes months and years to succeed if at all.   The section on cancer reminds me a lot of where we are going with Parkinson’s and trying to advance new paradigms in the treatment and curative strategies.  Professionally, I have even decided  to pursue research funding in the area of Parkinson’s disease.   Why not spend the rest of my academic career studying my own disease; in the least I can help educate others about this disorder. Furthermore, I can assure you from my reading and meeting people over the last couple of years, there are many hundreds of scientists and clinicians throughout this world studying Parkinson’s and trying to advance our understanding and derive a cure.  I see their devotion, I see their commitment to helping cure our disorder.

The science behind Parkinson’s is quite complicated. These complications suggest that Parkinson’s may be more of a syndrome rather than a disease. Instead of a one-size-fits-all like a disease would be classified; Parkinson’s as a syndrome would be a group of symptoms which consistently occur together.  What this might imply is that some treatment strategy might work remarkably well on some patients but have no effect on others. However, without a detailed understanding and advancement of what Parkinson’s really is we will never reach the stage where we can cure this disorder.

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In a recent blog from the Science of Parkinson’s disease, Simon nicely summarized all the current research in 2017 in Parkinson’s disease (click here to read this post). To briefly summarize what he said is that there are multiple big Pharma collaborations occurring to study Parkinson’s.  There are more than 20 clinical trials currently being done in various stages of completion to prevent disease progression but also to try to cure the disorder.  From a search of the literature, there are literally hundreds of research projects going on that promise to advance our understanding of this disorder. With the last point, it still will take time to happen. Finally, I am a realist but I’m also optimistic and positive that we’re making incredible movement toward much better therapies, which will eventually lead to curative options for Parkinson’s.

And a final analogy to baseball and Parkinson’s, as Tommy Lasorda said “There are three types of baseball players: those who make it happen, those who watch it happen, and those who wonder what happens.”  I really want to be one of those scientists that help make it happen (or at least to help advance our understanding of the disorder).

“You can’t expect life to play fair with your heart or your brain or your health. That’s not the nature of the game we call life. You have to recognize the nature of the game and know that you can do your best to make the right choices, but life if going to do whatever the hell it pleases to you anyway. All you can control is how you react to whatever life throws at you. You can shut down or you can soar.” Holly Nicole Hoxter

Cover photo credit: PNC Park photo: i.imgur.com/32RWncK

Sign post scienceofparkinsons.com/

“Go the Distance” With MAO-B Inhibitors: Potential Long-term Benefits in Parkinson’s

“Life is 10 percent what you make it, and 90 percent how you take it.” Irving Berlin

“My attitude is that if you push me towards something that you think is a weakness, then I will turn that perceived weakness into a strength.” Michael Jordan

Précis:  (1) A brief review of the major classes of therapeutic compounds for treating Parkinson’s. (2) Defining clinical trials.  (3) Hauser et al.(Journal of Parkinson’s Disease vol. 7, no. 1, pp. 117-127, 2017) report that Parkinson’s patients who received an MAO-B inhibitor for a long period of time had statistically significant slower decline in their symptoms compared to patients not on an MAO-B inhibitor (click here to see paper). (4) Addendum: “New Kid In Town”, The FDA approves another MAO-B inhibitor named Xadago (safinamide). 

Pharmacological treatment of Parkinson’s [Please note that these views and opinions expressed here are my own. Content presented here is not meant as medical advice. Definitely consult with your physician before taking any type of drug.]: The management of Parkinson’s is broadly divided up into motor and non-motor therapy.  A brief description of the therapy for motor dysfunction will be presented here.  Please see the drawing below for an overview.   Within the framework of treating someone with Parkinson’s you must consider managing their symptoms with the hope that some compound might possess either  neuroprotective or neurorestorative actions. To date, we do not have a cure for Parkinson’s but the study described below suggests an existing compound may be neuroprotective when used for a long  time.

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“Things turn out best for the people who make the best of the way things turn out.” John Wooden

Medical management of the motor-related symptoms of Parkinson’s:

Levodopa, together with carbidopa, is the ‘gold standard’ of treatment of motor signs and symptoms. Carbidopa is  a peripheral decarboxylase inhibitor (PDI), which provides for an increased uptake of levodopa in the central nervous system. As shown above, levodopa (denoted as L-DOPA) is converted to dopamine by the dopaminergic neurons. Levodopa is still the most effective drug for managing Parkinson’s motor signs and symptoms. Over time, levodopa use is associated with issues of “wearing-off” (motor fluctuation) and dyskinesia.  For further information about levodopa and dopamine, please see this previously posted topic (click here).

Catechol-O-methyl transferase (COMT) inhibitors prolong the half-life of levodopa by blocking its metabolism. COMT inhibitors are used primarily to help with the problem of the ‘wearing-off’ phenomenon associated with levodopa.

Dopamine agonists are ‘mimics’ of dopamine that pass through the blood brain barrier to interact with target dopamine receptors. Dopamine agonists provide symptomatic benefit and delay the development of dyskinesia compared to levodopa.  Dopamine agonists are not without their own side-effects, which can occur in some patients, and include sudden-onset sleep, hallucinations, edema, and impulse  behavior disorders.  For more information about dopamine agonists,  please see this previously posted (click here).

Finally, monoamine oxidase (MAO)-B is an enzyme that destroys dopamine; thus, MAO-B inhibitors help prevent the destruction of dopamine in the brain. MAO-B inhibitors have some ability to reduce the symptoms of Parkinson’s. The most common severe side effects of MAO-B inhibitors include constipation, nausea, lightheadedness, confusion, and hallucinations.  There may also be contraindications between MAO-B inhibitors with other prescription medications,  vitamins, and certain foods/drinks (e.g., aged cheese and wine). Definitely talk to your doctor and pharmacist about potential drug interactions if you are considering an MAO-B inhibitor in your therapeutic regimen.

“You should just do the right thing.” Dean Smith

What are clinical trials? The simple description is that a clinical trial determines if a new test or treatment works and is safe. The National Institutes of Health (NIH) defines a clinical trial (paraphrased here) as a research study where human subjects are prospectively assigned1 to one or more interventions2 (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.[1The term “prospectively assigned” refers to a predefined process (e.g., randomization) in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.2An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.  3Health-related biomedical or behavioral outcome is defined as the prespecified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.]  For the complete NIH definition, please click here.

As described by ‘ClinicalTrials.gov’, clinical trials are performed in phases; each phase attempts to answer a separate research question. Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.Phase III:  The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use. A more complete description is included here (click here).

What is important to remember is that clinical trials are experiments with unknown outcomes that must follow a rigorous approach to safely evaluate and possibly validate potential treatments.

“Nothing has ever been accomplished in any walk of life without enthusiasm, without motivation, and without perseverance.” Jim Valvano

NET-PD-LS1 clinical trial went bust on creatine use in treating Parkinson’s: The NET-PD-LS1 clinical trial went from March 2007 until July 2013. NET-PD-LS1 was a multicenter, double blind, placebo-controlled trial of 1741 people with early Parkinson’s. The goal of NET-PD-LS1 was to determine if creatine could slow long-term clinical progression of Parkinson’s (to learn more about this clinical trial go here or go here) . NET-PD-LS1 was one of the largest and longest clinical trials  on Parkinson’s . This clinical trial was stopped after determining there was no benefit to using creatine to treat Parkinson’s.

“It’s what you learn after you know it all that counts.” John Wooden

NET-PD-LS1 clinical trial gets a ‘gold star’ for MAO-B inhibitors in treating Parkinson’s: NET-PD-LS1 was  a thorough and well organized clinical trial.  New results have been published in a secondary analysis of the clinical trial to determine if MAO-B inhibitors for an extended time affected the symptoms of Parkinson’s. Almost half (784) of the patients in NET-PD-LS1 took an MAO-B inhibitor. The MAO-B inhibitors used in NET-PD-LS1 were Rasagiline (Brand name Azilect) and Selegiline (Brand names Eldepryl, Zelapar, or EMSAM).  More than 1600 of the patient’s completed both baseline and one year evaluation/assessment measuring changes in their symptoms (this was done using a combination of five different measurement scales/systems).  Their results were exciting; the patients that were taking an MAO-B inhibitor for a longer time (1 year) had a slower clinical decline (~20% benefit in the magnitude of the decline compared to the patients not taking an MAO-B inhibitor).  These results indicate that MAO-B inhibitors  somehow are able to slow the progression of the symptoms of Parkinson’s.

“Always look at what you have left. Never look at what you have lost.” Robert H. Schuller

Does this prove that MAO-B inhibitors are neuroprotective in Parkinson’s?   The hopeful person inside of me  wants this answer to be yes; however, the scientist that also resides inside of me says no not quite yet.  The goal of neuroprotection is to slow or block or reverse progression of Parkinson’s; and by measuring changes in dopamine-producing neurons.  Early basic science results with MAO-B inhibitors found some neuroprotection in model systems. This new publication reignites the storyline that MAO-B inhibitors are potentially neuroprotective.

“Efforts and courage are not enough without purpose and direction.” John F. Kennedy

A personal reflection about the strategy for treatment of Parkinson’s: MAO-B inhibitors have never been part of my strategy for treating my disorder. I have been using a traditional drug therapy  protocol [Sinemet and Ropinirole] (click here),  supplemented by a  relatively comprehensive CAM approach (click here), bolstered hopefully by a neuroprotective (experimental) agent [Isradipine] (click here), and fortified with as much exercise in my day that my life can handle (click here).  However, there is a constant and dynamic flux/flow of ideas regarding treatment options for Parkinson’s. Thus,  my strategy for treating my disorder needs to be fluid and not fixed in stone. Over the next few weeks, I will be reading more about MAO-B inhibitors, having some serious conversations with my Neurologist and Internist,  with my care partner assessing the risk and benefits of taking an MAO-B inhibitor, and coming up with a consensus team opinion about whether or not I should start taking an MAO-B inhibitor.

Addendum- FDA Approves Xadago for Parkinson’s Disease:
As the Eagles sing in New Kid In Town, “There’s talk on the street; it sounds so familiar / Great expectations, everybody’s watching you”. The first new drug in a decade to treat Parkinson’s is an MAO-B inhibitor named Xadago (Safinamide).  This drug has an interesting past with the FDA before getting approved this week. Is it different? Xadago is for patients using levodopa/carbidopa that are experiencing troublesome “off episodes”, where their symptoms return despite taking their medication. Thus, Xadago is being marketed as an add-on therapy, which is different than existing MAO-B inhibitors because they can be used as stand alone monotherapy. In two separate clinical trials for safety and efficacy of Xadago, compared to patients taking placebo, those taking Xadago showed more “on” time and less “off” time. Interestingly, this is exactly what you’d expect for an MAO-B inhibitor  (sustaining dopamine, see drawing above).  The most common adverse side-effects reported were uncontrolled involuntary movement (side-note: isn’t this what we’re trying to prevent in the first place?), falls, nausea, and insomnia. Clearly, taking Xadago with another MAO-B inhibitor would not be good. Xadago joins a list of other MAO-B inhibitors that are FDA approved for Parkinson’s including Selegiline (Eldepryl, Zelapar, EMSAM) and Rasagiline (Azilect). Whether the efficacy of Xadago is different or improved from existing MAO-B inhibitors remains to be shown; however, having another MAO-B inhibitor may allow Parkinson’s patients the possibility to use the one with the least adverse reactions.  Clearly, close consultation with your Neurologist will be very important before adding any MAO-B inhibitor to your daily arsenal of drugs.  The good news is now you’ve got another option to join the stable of possible MAO-B inhibitors to be used with levodopa/carbidopa.

For the background/rationale behind using “Go the distance” in the title, watch this video clip: Field of Dreams (3/9) Movie CLIP – Go the Distance (1989) HD by Movieclips  (click here to watch Go the Distance).

“Only the mediocre are always at their best. If your standards are low, it is easy to meet those standards every single day, every single year. But if your standard is to be the best, there will be days when you fall short of that goal. It is okay to not win every game. The only problem would be if you allow a loss or a failure to change your standards. Keep your standards intact, keep the bar set high, and continue to try your very best every day to meet those standards. If you do that, you can always be proud of the work that you do.” Mike Krzyzewski

Cover photo image: https://img1.10bestmedia.com/Images/Photos/304499/Pier-orange-sky-compressed_54_990x660.jpg

Dopamine neurons for the drawing wermodified from http://www.utsa.edu/today/images/graphics/dopamine.jpg

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200 Years Ago James Parkinson published “An Essay On The Shaking Palsy”

“I have a form of Parkinson’s disease, which I don’t like. My legs don’t move when my brain tells them to. It’s very frustrating.” George H.W. Bush

“I discovered that I was part of a Parkinson’s community with similar experiences and similar questions that I’d been dealing with alone.” Michael J. Fox

Summary: Two hundred years ago in 1817, Dr. James Parkinson published “An Essay On The Shaking Palsy”, which was the first medical document to fully describe Parkinson’s disease  (please click here to read a full-length version of Parkinson’s essay). A short synopsis of the essay and his life are included here.

James Parkinson and his essay from 1817

Who was James Parkinson?   I’ve read several review articles about Dr. Parkinson,  and it is clear to me he was a very intelligent, passionate and compassionate person: “James Parkinson (1755–1824) worked as a general practitioner in the semi-urban hamlet of Hoxton, north east of the City of London, where he had been born, and where he lived all his life. The historian Roy Porter considered Parkinson a man ‘with impeccably enlightened credentials,’ a doctor with a highly developed empiricist bent, committed to observation and recording of the human and natural worlds, and faithful to social and political ideals including widening of the franchise and improvements in the material conditions of the majority of people. In addition to his daily work in general practice, James Parkinson was a public health reformer, an advocate of infection control in London workhouses, a medical attendant to a Hoxton madhouse, a writer of political pamphlets and children’s stories, a geologist and fossilist, and the author of a textbook of chemistry.” ( click here to read the full citation)

Review about Dr. Parkinson: (click here to read article), Morris, AD (April 1955). “James Parkinson, born April 11, 1755”. Lancet. 268 (6867): 761–3. PMID 14368866.

Title page to the essay: (click here for a nice historical perspective of Parkinson’s disease). Publication: Parkinson J. 1817. An essay on the shaking palsy. Whittingham and Rowland for Sherwood, Needly and Jones, London. .

Parkinson.paper

The Essay: Much has been written about the essay composed by Dr. Parkinson. Simply stated it is remarkably accurate in its depiction of Parkinson’s disease, which he called shaking palsy.   My goal in this post is not to exhaustively review his essay;  however, after reading this overview I hope you decide to read the essay. (Click here to read a full-length version of Parkinson’s essay).

 Definition of a new disease:  Dr. Parkinson described it as a disease that had an “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured.”   We know today that there are both motor and non-motor issues involved with Parkinson’s.

Knowledge that the patients were suffering:  Dr. Parkinson was most aware of what these patients were going through “the unhappy sufferer has considered it as an evil, from the domination of which he had no prospect of escape.”

Detailed and exacting description of the patients:  One of the more  interesting features about the essay is the detailed description of the six patients Dr. Parkinson observed: “So slight and nearly imperceptible are the first inroads of this malady, and so extremely slow its progress, that it rarely happens, that the patient can form any recollection of the precise period of its commencement. The first symptoms are a slight sense of weakness, with a proneness to trembling in some particular part; sometimes in the head, but most commonly in one of the hands and arms.” And here as well, “But as the malady proceeds, even this temporary mitigation of suffering from the agitation of the limbs is denied. The propensity to lean forward becomes invincible, and the patient is thereby forced to step on the toes and fore part of the feet, whilst the upper part of the body is thrown so far forward as to render it difficult to avoid falling on the face. In some cases, when this state of the malady is attained, the patient can no longer exercise himself by walking in his usual manner, but is thrown on the toes and forepart of the feet; being, at the same time, irresistibly impelled to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace. In some cases it is found necessary entirely to substitute running for walking; since otherwise the patient, on proceeding only a very few paces, would inevitably fall.”  Dr. Parkinson also noted there was a sleeping disorder component, “In this stage, the sleep becomes much disturbed. The tremulous motion of the limbs occur during sleep, and augment until they awaken the patient, and frequently with much agitation and alarm.”

Hope for a cure: After describing the six patients in his essay, Dr. Parkinson postulated whether or not there was going to be a cure for this new disease? “On the contrary, there appears to be sufficient reason for hoping that some remedial process may ere long be discovered, by which, at least, the progress of the disease may be stopped. It seldom happens that the agitation extends beyond the arms within the first two years; which period, therefore, if we were disposed to divide the disease into stages, might be said to comprise the first stage. In this period, it is very probable, that remedial means might be employed with success: and even, if unfortunately deferred to a later period, they might then arrest the farther progress of the disease, although the removing of the effects already produced, might be hardly to be expected.”   We’ve come a long way in two hundred years in our understanding of this disease; however, we’ve yet to cure Parkinson’s.

A new disease:  Dr. Parkinson was convinced he had described a new disease. As neurology evolved over the next several decades, others read the essay and agreed. Dr. Jean-Martin Charcot  (the acknowledged father of modern neurology) suggested that Dr. Parkinson’s name be linked to the disease he had so accurately described; thus, “maladie de Parkinson” (Parkinson’s disease).  For an additional summary on Parkinson’s disease, and the man behind the discovery please click here

Closing thoughts about Dr. Parkinson: Clearly, Dr. Parkinson was a most talented individual; he was driven to be a good physician and to be an observant scientist.  With  this attention to detail, he was the first to really accurately describe this disease. And  if that wasn’t enough, Dr. Parkinson had a fossil named after him  because  of his interest in geology and paleontology if you’re interested in additional aspects of his life please click and read this paper. I  encourage you to look through any of the papers cited here; you will gain tremendous respect for Dr. James Parkinson.

 To conclude, here are three quotes about Parkinson’s disease:
“realized while I was announcing myself to the group that I was conceding something profound: that the diagnosis marked an irreversible change in my identity, the moment that one version of me ended and another version” Jon Palfreman (Brain Storms: The Race to Unlock the Mysteries of Parkinson’s Disease)
•The next time you are imagining the worst, look up the definition of imagination.” Robert Lyman Baittie (Tremors in the Universe: A Personal Journey of Discovery with Parkinson’s Disease and Spirituality)
•”Without the quest, there can be no epiphany.” Constantine E. Scaros (Reflections on a Simple Twist of Fate: Literature, Art and Parkinson’s Disease)

 

Cover photo credit: https://s-media-cache-ak0.pinimg.com/originals/55/3d/2c/553d2ccd51dd6610cfa91939c4905b96.jpg

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