Management of Orthostatic Hypotension in Patients With Parkinson's Disease

Abstract

Orthostatic hypotension is common in Parkinson's disease. The current recommended management of orthostatic hypotension related to Parkinson's disease involves first general measures and then medications with little risk of severe adverse side effects.

Introduction

Neurogenic orthostatic hypotension is common in patients with Parkinson's disease. Perhaps, 30%–40% of patients with Parkinson's disease have orthostatic hypotension, and the prevalence rises with age, disease severity and disease duration.^[1,2] Orthostatic hypotension is defined as a drop in systolic blood pressure of ≥20 mm Hg or of diastolic blood pressure of ≥10 mm Hg, within 3 min of standing or upon head-up tilt (minimum 60°) on a tilt table.^[3]

In patients with Parkinson's disease, autonomic degeneration impairs the sympathetic response to baroreceptor input.^[4] During the course of Parkinson's disease, the accumulation of α-synuclein aggregates adds to the problems of neuronal degeneration and autonomic failure.^[5] Upon standing, many patients with Parkinson's disease cannot compensate for the venous pooling and reduced venous return caused by their compromised autonomic reflexes. Their subsequent drop in blood pressure causes presyncopal symptoms and difficulty in maintaining an upright posture.

The management of orthostatic hypotension in patients with Parkinson's disease is important because minimising this problem can improve cognition, balance and quality of life.^[6] Furthermore, treating orthostatic hypotension makes syncope less likely and so reduces the risk of falls and injury. Currently, the initial treatment is to remove iatrogenic causes (eg, antihypertensive medications) and to consider non-pharmacological interventions. Pharmacological interventions are needed only in a minority. In this review, we highlight both non-pharmacological and pharmacological options for managing orthostatic hypotension and analyse the extent to which these treatments help the problem.

Treatment

There are many therapeutic options for managing orthostatic hypotension in patients with Parkinson's disease. The currently recommended non-pharmacological (Table 1) and pharmacological (Table 2) treatment options are shown.

Non-pharmacological Management

Water and Salt. Drinking water and increasing salt intake increases plasma volume, which help to maintain blood pressure upon standing. The recommended daily intake of water is 1.5–2.0 L/day and of sodium chloride is 6–10 g.^[7] The salt may be incorporated into meals or taken as supplement tablets.

Increasing fluid intake has been shown to have a positive effect comparable to that of orthostatic hypotension medications^[8,9] and has only mild adverse outcomes (eg, urinary frequency). High-salt intake, on the other hand, must be monitored carefully because it may lead to cardiovascular complications and mortality.^[10]

Compression Stockings. The rationale for compression therapy is to reduce venous pooling in the lower extremities, to promote venous return and cardiac output. The categories of compression stockings include knee-length, thigh-length, full-length and abdominal compression. The current literature reports modest efficacy and inconsistencies in the degree and location of compression.

Table 3 summarises the effect of compression on postural drop in patients with orthostatic hypotension at baseline. Five of 14 patients with neurogenic orthostatic hypotension reported mild symptomatic relief with knee-length compression despite insignificant changes in blood pressure.^[11] Patients using thigh-length compression also reported modest symptom improvement.^[12] While abdominal compression appears to be the only treatment capable alone of significantly reducing orthostatic hypotension, full-length compression also significantly reduces postural drop. In the self-reported Special Symptom Scale questionnaire for Orthostatic Intolerance, patients reported relief of dizziness, weakness, visual disturbance and palpitation when using elastic lower limb stockings (hip 30–40 mm Hg to ankle 40–60 mm Hg) after wearing them for 1 month.^[13]

Although compression stockings provide orthostatic relief, there may be difficulty with compliance. Full-length compression stockings are uncomfortable and may be a burden to put on and wear. If the patient is able to comply, compression stockings should be incorporated in the treatment regimen for orthostatic hypotension. Ideally, abdominal compression should also be included because there is often considerable pooling in the splanchnic circulation.^[15] In our experience, patients prefer compression stockings that do not cover the feet.

Pharmacological Management

In most cases, pharmacological treatments are coadministered with non-pharmacological treatments. While medications can quickly alter blood pressure levels, their use needs careful monitoring to minimise adverse outcomes, particularly supine hypertension.^[16]

Fludrocortisone. Fludrocortisone acts as a systemic corticosteroid, increasing sensitivity to circulating catecholamine.^[17] When increasing water and salt intake is ineffective, fludrocortisone is the usual alternative way to increase plasma volume. Because fludrocortisone acts by intravascular volume expansion, its pressor effect is gradual. Fludrocortisone elevates both standing systolic and diastolic blood pressure,^[12,18] decreases orthostatic symptoms^[19] and lengthens the period that patients can stand without orthostatic symptoms.^[12]

Fludrocortisone, primarily used for adrenocortical insufficiency in both the USA and Europe, is a first-line monotherapy agent to manage orthostatic hypotension. The recommended dose is 0.1–0.2 mg/day, and it can take up to 5 days to see the full effects. Higher doses elevate circulating epinephrine, which can cause hypokalaemia and supine hypertension. Fludrocortisone is not recommended for patients with congestive heart failure or chronic renal failure.

Midodrine. Midodrine, a peripheral α-1 adrenoceptor agonist, exerts a pressor effect on both venous and arterial constriction^[20] and is effective 1 h after ingestion.^[21] The recommended dose (typically given in the morning, noon and afternoon to avoid supine hypertension in the evening) is up to 10 mg three times daily; each dose typically lasts for 4 h, consistent with blood levels of the active metabolite desglymidodrine.^[22]

In double-blind studies, midodrine gave a dose-dependent increase in mean standing systolic blood pressure and resulted in significantly higher mean global improvement of orthostatic symptoms scores compared with placebo.^[21,22] Midodrine's major limitation is supine hypertension but this adverse reaction may be minimised by taking it immediately before starting upright activities and avoiding it before becoming supine. Other potential side effects include piloerection, itchiness and urinary retention.^[23]

In 2010, the US Food and Drug Administration (FDA) almost withdrew midodrine due to limited postmarketing trials. However, patient and physician lobbying proved successful in reversing the FDA's decision. Currently, midodrine is one of the two antihypotensive drugs approved by the US FDA. In the UK, midodrine is currently not licensed for managing orthostatic hypotension but is considered a second-line drug that may be used either as monotherapy or combined with fludrocortisone. Despite moderate quality of evidence in meta-analyses, subjective reporting on midodrine appears to be compelling enough to maintain midodrine as a therapeutic option. Ongoing clinical trials are currently being conducted to examine its long-term efficacy.

Droxidopa. Droxidopa (L-threo-dihydroxyphenylserine) is a synthetic prodrug that is converted into norepinephrine by the ubiquitous enzyme dopa-decarboxylase. In numerous trials conducted in Japan and Europe, droxidopa decreased postural drop in patients with orthostatic hypotension.^[24,25] Smaller studies and clinical trials in the USA also showed that droxidopa reduced orthostatic symptoms.^[26,27] In a recent phase III clinical trial, droxidopa improved Orthostatic Hypotension Symptom Assessment and Orthostatic Hypotension Daily Activity Scale in patients with neurogenic orthostatic hypotension.^[28] In a double-blind study with 225 patients with Parkinson's disease, droxidopa treatment increased standing systolic blood pressure, reduced dizziness upon standing and reduced the number of falls.^[29]

An open-label study reported that droxidopa was safe and well tolerated by patients with symptomatic neurogenic orthostatic hypotension.^[30] Furthermore, it did not significantly increase supine blood pressure in the evening, thereby minimising the risk for supine hypertension overnight.^[31] Due to its high tolerance and efficacy in improving orthostatic hypotension with a lower risk of supine hypertension, droxidopa has become a promising agent for managing orthostatic hypotension in patients with Parkinson's disease. Earlier this year, the US FDA approved droxidopa as an antihypotensive agent under the accelerated approval programme. Although droxidopa is still undergoing phase III clinical trials in Europe, growing evidence behind its efficacy supports its use as an alternative to fludrocortisone and midodrine.

The US FDA-recommended dose is 100 mg three times daily, although a dose titration study has reported 300 mg three times daily to be the optimal dosage.^[25] Because patients with Parkinson's disease commonly take dopa-decarboxylase inhibitors to counter hyperdopaminergia induced by L-dopa treatment, dose adjustments for droxidopa may be required. However, the efficacy of droxidopa is not diminished when coadministered with the dose (25 mg for 100 mg L-dopa) of dopa-decarboxylase inhibitor typically used in the treatment of Parkinson's disease.^[32]

Pyridostigmine. Pyridostigmine is a cholinesterase inhibitor that potentiates cholinergic transmission when the autonomic ganglia have already been engaged. Therefore, administering pyridostigmine as needed may mediate orthostatic hypotension without contributing to supine hypertension. Clinical trials to date have shown modest efficacy.

In an early open-label trial, 60 mg pyridostigmine orally increased standing blood pressure and reduced orthostatic symptoms in 15 neurogenic orthostatic hypotension patients.^[33] A follow-up double-blind crossover study showed that pyridostigmine (60 mg) alone or coadministered with midodrine gave results consistent with the initial open-label trial.^[34] Despite a modest increase in standing blood pressure, midodrine provided more salient symptomatic relief. One patient reported remission of symptoms after replacing midodrine with pyridostigmine.

While pyridostigmine offers a promising clinical benefit in the global improvement of orthostatic symptoms, the use of pyridostigmine as treatment is limited by undesirable side effects, including frequent abdominal cramping, nausea and vomiting.^[35] It may, however, reduce constipation in patients with Parkinson's disease. We need further exploration in its mechanism of action, dose-dependent effects and long-term implications.

Domperidone. While dopamine agonists are widely used to manage Parkinson's symptoms, one major side effect is acute orthostatic hypotension after starting the treatment.^[36] Domperidone is a peripheral dopamine D2 receptor antagonist that is effective in treating acute orthostatic hypotension induced by dopamine agonists.^[37]

In one double-blind crossover study on patients with idiopathic Parkinson's disease, domperidone 10 mg three times daily was more effective than fludrocortisone in reducing postural drop.^[12] The patients taking dopamine agonists also preferred domperidone to fludrocortisone.

While domperidone appears a promising treatment of acute orthostatic hypotension induced by dopamine agonist therapy, its mechanism of action still remains to be elucidated. Domperidone is contraindicated in patients with underlying cardiac conditions because its use increases the risk of prolonged QT syndrome.^[38]

Yohimbine. Yohimbine, an α-2 adrenergic antagonist, centrally activates the sympathetic response and promotes norepinephrine release.^[39] This pressor effect enhances residual sympathetic tone.^[40]

In an open-label trial, a 5.4 mg dose of oral yohimbine increased both seated and standing blood pressure.^[41] The increase in the seated blood pressure was the greater. In a more recent crossover study that included Parkinson's disease cases, the same dose of yohimbine reduced lightheadedness and increased standing diastolic blood pressure.^[42]

To enhance the pressor response in these patients, an alternative treatment may involve the coadministration of yohimbine with a norepinephrine transporter inhibitor. Atomoxetine selectively inhibits the norepinephrine transporter, thereby increasing synaptic norepinephrine concentration. Coadministering yohimbine with atomoxetine can then enhance the pressor effect of atomoxetine by potentiating the activity of the remaining sympathetic efferent fibres that have not yet degenerated. In a crossover study using 17 patients with severe peripheral autonomic failure, the combination of oral yohimbine (5.4 mg) with atomoxetine (18.0 mg) synergistically increased seated systolic blood pressure and improved orthostatic symptoms, whereas yohimbine and atomoxetine alone did not.^[43] The results of this preliminary study are promising, but the duration of the pressor effects and safety of this treatment option require further study. While yohimbine is undergoing phase III trials in the USA, it is not recognised as an antihypotensive agent in Europe.

Summary and Recommendations

In our experience, managing orthostatic hypotension in patients with Parkinson's disease is clinically helpful because it improves their motor and cognitive function and further enhances their quality of life. Management of orthostatic hypotension should initially involve physiological countermeasures, such as reducing non-antihypertensive medication, increasing water and salt intake and compression therapy. If medications are needed, they may be selected based on symptom severity and side effect profile.

http://www.medscape.com/viewarticle/841709?src=wnl_edit_tpal

Potential treatment target identified for rare form of diabetes, other disorders

June 24, 2015

Cell death can trigger numerous diseases, including a rare and severe form of diabetes known as Wolfram syndrome. The cascade of cell death occurs when molecules spill from one part of a cell into another where they don't belong.

Now, scientists working to find treatments for Wolfram syndrome have identified a gatekeeper that prevents those harmful molecules from spilling and triggering cell death. The researchers, at Washington University School of Medicine in St. Louis, also have found that the gatekeeper -- an enzyme -- may be a good treatment target not only for diabetes but for some heart problems, Parkinson's disease and other disorders caused by the same type of cellular stress that can lead to cell death.

The findings are available June 23 in the journal Science Signaling.

'The type of cell stress involved in Wolfram syndrome, as well as more common forms of diabetes, can contribute to multiple diseases,' said principal investigator Fumihiko Urano, M.D., Ph.D., the Samuel E. Schechter Professor of Medicine. 'We believe the enzyme we identified may provide us with a target to protect many types of cells from a death cascade that leads to those different, seemingly unrelated disorders.'

Studying cells from mice, the research team found that the gatekeeper enzyme -- known as IRE1 -- beefed up the membrane of a cellular structure called the endoplasmic reticulum, preventing damaging molecules from spilling into other parts of the cell.

'These molecules are supposed to stay in specific locations,' Urano said. 'Sometimes a molecule may travel to different parts of the cell to perform a function, but it needs to return to the place it resides, or big problems can result.'

Cell death can result if there are inadequate levels of the enzyme that keeps potentially harmful molecules in the proper place.

Urano explained that if cells experiencing stress related to dysfunctional IRE1 enzymes are insulin-secreting cells, a person will develop diabetes. If cardiac cells experience that problem, an individual may develop heart disease, he said. And if the cells experiencing such stress are in the brain, disorders such Parkinson's disease or the neural damage related to Wolfram syndrome may occur.

Urano's team found that by replacing or enhancing the enzyme in mouse cells, they strengthened the cellular membrane, stopped molecules from leaking into other parts of a cell and prevented cell death. Now they want to prove that the enzyme plays an identical role in human cells.

He said it may be possible to treat Wolfram syndrome and other disorders with compounds that target the enzyme.

'It's clear from our experiments that this enzyme can keep the membrane in the cell from becoming permeable and leaking,' Urano said. 'We think it may be possible to prevent Wolfram syndrome and other diseases related to this type of cellular stress by targeting the enzyme to make the membrane stronger.'

Later this summer, Washington University and St. Louis Children's Hospital will host the sixth annual Wolfram syndrome clinic for patients from around the world. Urano and his colleagues will collect and test blood samples to see whether they can find markers of IRE1 dysfunction in patients with the disorder.

http://www.medicalnewstoday.com/releases/295813.php?tw

Clinician-scientist who developed Parkinson's disease breakthrough is awarded the 2015 Taubman Prize

Clinician-scientist who developed Parkinson's disease breakthrough is awarded the 2015 Taubman Prize

The 2015 Taubman Prize goes to Mahlon DeLong, M.D.

ANN ARBOR, Mich., June 24, 2015 /PRNewswire-USNewswire/ -- 

A physician-scientist whose work has improved quality of life for tens of thousands of Parkinson's disease patients is the recipient of the 2015 Taubman Prize for Excellence in Translational Medical Science, the University of Michigan's A. Alfred Taubman Medical Research Institute announced. 

Mahlon DeLong, M.D., Professor of Neurology at the Emory University School of Medicine, will receive the $100,000 prize in recognition of his contributions to the treatment of Parkinson's disease.

DeLong's research – spanning a 40-year career in medicine and science – identified the anatomical brain circuits involved in the clinical features of Parkinson's disease and a novel target for surgical intervention, the subthalamic nucleus, a portion of the basal ganglia, brain structures located deep in the brain.

This finding paved the way for the application of high frequency deep-brain stimulation (DBS) of the subthalamic nucleus, a technique now used worldwide for advanced Parkinson's disease patients.  More than 100,000 individuals have received the treatment, which suppresses tremor and other motor impairments, and improves the ability to carry out the normal activities of daily living.

"Dr. DeLong's contribution to improved care and quality of life for patients with devastating movement disorders is remarkable," said Eva Feldman, M.D., Ph.D., director of the Taubman Institute, and a professor at the U-M Medical School.  "He exemplifies the ethos of the dedicated clinician-scientist.  We are honored to recognize his extraordinary contributions by awarding him the Taubman Prize."

DeLong was selected by a national panel of eminent medical science experts from among dozens of nominees for the Taubman Prize.  Over decades he and his colleagues have mapped brain activity and deciphered the complex pathways and circuitry involved with the processing of motor functions, thoughts and emotions.  Insights gained through his basic research, animal models and experiments eventually led to a clearer understanding of the abnormalities in brain circuits in animal models of Parkinson's and how interruption of a key portion of the motor circuits could dramatically improve clinical features. 

DeLong's studies contributed greatly to the revival of surgical approaches for treating movement disorders. 

The development of the novel technique of high frequency deep-brain stimulation, using implanted electrodes, by Dr. Alim Louis Benabid in Grenoble, France, when applied to the subthalamic nucleus in patients with Parkinson's produced a similar result as surgical interruption.   DBS, because of its less invasive, reversible and adjustable features, rapidly replaced direct, irreversible destructive lesioning approaches.

DeLong, the William Timmie Professor of Neurology at Emory University School of Medicine, will present the keynote address at the Taubman Institute's annual symposium on Oct. 16, 2015 at the Kahn Auditorium on the U-M medical campus.  The symposium is open to the general public. 

The Taubman Prize was established in 2012 to recognize outstanding translational medical research beyond the University of Michigan.  It includes a $100,000 award and is presented each year to the non-U-M clinician-scientist who has done the most to transform laboratory discoveries into clinical applications for patients suffering from disease.

Previous recipients are:

2014: Carl June, M.D., of the Perelman School of Medicine at the University of Pennsylvania, for discoveries related to immunotherapy for leukemia using patients' own T cells.

2013: Brian Druker, M.D., of the Oregon Health & Science University and Charles Sawyers, M.D., of Memorial Sloan Kettering Cancer Center, for their discoveries related to chronic myeloid leukemia.

2012:  Hal Dietz, M.D., of Johns Hopkins University for his discoveries related to connective tissue disease.

About Mahlon DeLong, M.D.:  DeLong is a key faculty leader of The Jean and Paul Amos Parkinson's Disease and Movement Disorders Research Program. He also is co-director and founder of ENTICe (Emory Neuromodulation and Technology Innovation Center), whose goal is to foster advancement of neuromodulation and the development of innovative neuromodulation technologies for the treatment of neurological and psychiatric disorders.

He is a member of the Institute of Medicine, a fellow of the American Academy of Arts and Sciences, a fellow of the American Association for the Advancement of Science (AAAS), an elected member of the Johns Hopkins Society of Scholars.  He is scientific director of the Dystonia Medical Research Foundation and a member of the Scientific Advisory Board of the American Parkinson Disease Association.

DeLong received his undergraduate degree from Stanford University and his medical degree from Harvard University. He worked as a researcher at the National Institute of Mental Health at the National Institutes of Health (1968-1973) completed his residency in Neurology at Johns Hopkins School of Medicine and was a member of the Johns Hopkins faculty (1975-1989). In 1989 he joined Emory University School of Medicine, where he served as chair of the Department of Neurology (1989-2003).

DeLong has received numerous awards including the 2013 Breakthrough Prize in Life Sciences and the 2014 Lasker Award, which recognizes excellence in research aimed at curing intractable diseases and extending human life. He also received the 2009 American Academy of Neurology Movement Disorders Research Award and the 2008 Movement Disorders Society Lifetime Achievement Award.

He is a member of the Institute of Medicine, a fellow of the American Academy of Arts & Sciences, a fellow of the American Association for the Advancement of Science (AAAS), an elected member of the Johns Hopkins Society of Scholars, and is a past chair of the Society for Neuroscience. He is scientific director of the Dystonia Medical Research Foundation and a member of the Scientific Advisory Board of the American Parkinson Disease Association.

About the A. Alfred Taubman Medical Research Institute:  In 2007 Michigan businessman, philanthropist and noted patron of the arts A. Alfred Taubman provided the initial funds to establish the institute bearing his name at the University of Michigan Medical School. Its mission is to provide the university's finest medical scientists the freedom, resources and collaborative environment they need to push the boundaries of medical discovery, to produce breakthroughs in cures to speed the development of effective treatment for some of the most devastating illnesses. Currently, nearly 40 Taubman Scholars are advancing their research with the assistance of grants from the institute.

http://health.einnews.com/article/272536918/l5UFedZ2uXfI2MpZ

Subcutaneous Levodopa Infusion Smooths Blood Levels in PD

Daniel M. Keller, PhD

June 22, 2015

Both ND0612L and ND0612H produced steady, therapeutic LD plasma levels, with the H preparation producing about three-fold higher plasma concentrations than the L preparation. Adjunctive entacapone increased the steady-state levels with both formulations by about 25% without affecting the fluctuation index.

Dr Oren noted that safety and tolerability of ND0612 were good. Eight patients reported a total of 10 treatment-emergent adverse effects. One patient in the ND0612H group had an elevation of liver enzymes considered possibly related to the treatment. Most patients did have positive results on Draize tests, indicating mild infusion site erythema and edema, which resolved.

Dyskinesia was not a problem. "It's an 8-hour infusion," Dr Oren said. "We didn't have any dyskinesia."

In a 6-month safety follow-up, all patients had relatively small infusion site nodules that resolved in 4 to 6 months. Interestingly, although the ND0612H group had twice the number of infusion sites and a higher infusion rate as the ND0612L group, the groups did not have any major difference in the number of nodules.

Previous exploratory efficacy analyses have shown that ND0612L reduced daily "off" time by more than 2 hours from baseline and improved sleep quality, quality of life, and clinical global impression of change scores Advantage of Subcutaneous Route

Dr Oren noted that delivery of LD by subcutaneous infusion may have an advantage over more invasive surgical procedures for treating PD.

"We have a patent on the way to do a liquid formulation as opposed to Duopa [LD/CD, Abbvie], for example, that is not a liquid formulation but a semisolid gel…that cannot be administered parenterally," she said.

Duopa is infused enterally directly into the jejunum through an implanted jejunostomy tube. The NeuroDerm device holds 6 or 12 mL and is fairly small, about the size of an insulin pump, in contrast to the Duopa device, which is larger and can hold a 100-mL cassette.

She said the ND0612L formulation is now going into phase 3 trials.

Maurizio Facheris, MD, senior associate director for research programs at the Michael J. Fox Foundation for Parkinson's Research, commented on the findings for Medscape Medical News.

"What I think is striking is truly having that flat pharmacokinetic in blood, specifically in the later stage of disease where your dopaminergic neurons are so much reduced and potentially the serotonergic neuron reuptake of levodopa and transforming it into dopamine," he said. "So the synchronization between the pharmacokinetic of the blood and the brain becomes important.... So that's what I like about this specific program."He noted that with the low dose, coadministration of entacapone was necessary to reach therapeutic LD levels.

"With the higher dose…you can see from the data that [they] are able to get closer to what the normal range would be," he said.

There is some debate as to whether patients should receive infusion-type LD therapies before getting surgery for implantation of a deep-brain stimulation (DBS) device.

"I do think that [this] would be a logical step to go before getting into DBS… Unlike [Duopa] intestinal gel, this is actually less invasive," Dr Facheris said.

The trial was sponsored by NeuroDerm (Rehovot, Israel). Dr Oren is an employee of the company. Dr Facheris is an employee of the Michael J. Fox Foundation for Parkinson's Research. The foundation supported early development of ND0612L.

http://www.medscape.com/viewarticle/846798?src=wnl_edit_tpal#vp_2

Urinary Problems in Parkinsonism Patients with A.Q. Rana MD, Educator Ne...

Runner With Parkinson's Disease Qualifies for Boston Marathon

Michael Westphal stumbled to the ground near the finish of The Great Run marathon.

June 23, 2015

Mchael Westphal, who was diagnosed with Parkinson's disease in 2006, finished The Great Run marathon in 3:32. 

He clocked 3:32:56, a time fast enough to qualify him for the Boston Marathon. Westphal’s efforts also helped him raise $32,800 for the Michael J. Fox Foundation. The sum far exceeded his original goal of $4,000.

 
Wesphal said the feeling of finishing the race went “beyond the runner’s high. It was one of those things that only happens a few times in your life, if you’re lucky.” 

In an email to Runner’s World Newswire, he wrote, “Although I did fall twice, the cheering crowd, the chalk writing on the roads by the island school children that read ‘Go Mike!’, and the knowledge that I was going to uphold my end of the bargain with my fundraising donors was an overwhelming feeling of happiness that’s hard to describe.” 

A competitive runner in high school and college, Westphal decided to take a long hiatus from running in 1994 to focus on his job. He was diagnosed with Parkinson's disease in 2006 and believed he'd never be able to run again. But last summer, he was inspired to try to return to the roads after witnessing Allen complete two 500-plus-mile treks throughout the U.S. 

Wesphal soon discovered his Parkinson’s symptoms dissipated while he ran, so he put The Great Run marathon on his calendar and began training in earnest. His main goal was to get to the starting line injury free. If he accomplished that, Westphal said he just wanted to finish. 

“I had donations of over $32,000, which averaged over $1,200 per mile,” Westphal wrote. “I wanted to make every mile count. There was a little bit of pressure not to disappoint.” 

Last month, he completed a 17-mile run at 7:32-per-mile pace, which, if he could keep it up for 26.2 miles, would put him well under the 3:40 mark to earn him a bib for the Boston Marathon. But qualifying wasn’t really on his radar until the middle of the race. 

“Once I started cranking along at a faster pace between 10 and 20 miles, I quit looking at my watch and ran according to how I felt,” Westphal wrote. “Coupled with the knowledge that I was far exceeding BQ pace by just feeling the miles fly by, I knew I could finish the race as long as I kept hydrated and wouldn’t be waylaid by unexpected heat stroke.”

At the 20-mile mark, Wesphal took a dose of carbidopa/levodopa, a synthetic dopamine-replacement medication that would help his muscles fire. 

“I think the one and only low point [of the race] was having to slow down and walk a few times because of the low dopamine levels in my body,” Westphal said. “I think [the medication] didn’t kick in because of the large volume of fluids I was drinking.” 

Westphal thinks the issue was “hit or miss” and that he could run much faster if he can get his dopamine levels under control. He plans to run the Mount Desert Island Marathon in Bar Harbor, Maine, in October and said there’s a good chance he’ll run the Boston Marathon next year.  

“I have a slight feeling of regret of not continuing to compete through my late 30s and 40s, and I wonder how much faster I could be now if I didn’t have Parkinson’s,” Westphal said. “But you live with those decisions and the card you are dealt and focus on what you are doing with your life now. You can still make that magic happen with some passion of your own.”

http://www.runnersworld.com/general-interest/runner-with-parkinsons-disease-qualifies-for-boston-marathon