Autonomic Dysfunction in Parkinson’s Disease

Published on January 19, 2015   67 min
0:00
My name is Ron Pfeiffer. I'm a professor and vice chair of the Department of Neurology at the University of Tennessee Health Science Center in Memphis. I have been interested in treating and performing research on patients with Parkinson's disease for almost 40 years. So it's a real delight today to be able to provide an overview of autonomic dysfunction in Parkinson's disease, which is a subject near and dear to my heart.
0:28
Parkinson's disease traditionally has been considered to be a motor disorder, characterized primarily by tremor, rigidity, and bradykinesia, with the later development of postural instability with balance impairment and falling. However, in the past 20 or more years, it's been increasingly recognized that Parkinson's disease contains much more than just motor dysfunction and that there are a broad array of features of Parkinson's disease that have little or nothing to do with motor function or dysfunction. These so-called nonmotor features include abnormalities of sensation, behavioral changes, sleep disorders, fatigue, and for our purposes today, autonomic dysfunction.
1:16
Virtually the entire array of autonomic function can be and is impaired in individuals with Parkinson's disease, including cardiovascular, gastrointestinal, urinary, sexual, and thermoregulatory dysfunction. And in the talk today, we will touch on each of these areas.
1:36
Over a decade ago now, we surveyed our clinic patients using a simple, non-validated questionnaire and found that when one looked at the various aspects of autonomic dysfunction, virtually in every instance, individuals with Parkinson's disease described more symptoms of autonomic dysfunction than did controls, who were primarily spouses. And if you summed those symptoms together, the difference, as you can see over in the right-hand column, became quite striking.
2:12
Much more recently, Khoo and colleagues, utilizing a much larger number of patients and utilizing a validated questionnaire, discovered virtually the same thing, in that individuals with Parkinson's disease demonstrated a markedly increased tendency to have autonomic dysfunction as part of their Parkinsonian picture with involvement of the gastrointestinal tract, urinary tract, sexual function, and cardiovascular function.
2:50
So let's start on our survey with cardiovascular dysfunction.
2:58
It has been clearly demonstrated that in individuals with Parkinson's disease, cardiac sympathetic denervation is present. Orimo and his colleagues demonstrated this quite elegantly utilizing immunohistochemical methods. In the panels at the bottom of this slide, you can see that both in the higher powered picture, C in the lower left, and the lower powered picture, D in the lower right, there is a profuse abundance of yellow fibers that are positive for tyrosine hydroxylase and nuerofilament and thus represent cardiac sympathetic fibers. This contrasts rather starkly with an individual with Parkinson's disease in the two panels above, both at lower and higher power, where these tyrosine hydroxylase-containing fibers are virtually absent, indicating the presence of marked cardiac sympathetic denervation.
4:01
This can be evaluated in living individuals with Parkinson's disease by utilizing I-123-metaiodobenzylguanidine, or MIBG, scintigraphy. MIBG is an analog of guanethidine, and it is handled very much like norepinephrine with regard to uptake and storage. Therefore, it can be utilized as a noninvasive assessment of cardiac sympathetic nerve endings. When it is administered to individuals, it is taken up in the heart, and of course, in other tissue, including the liver. And one can then measure the amount of uptake, contrasting it classically with uptake in the mediastinum. In the panel on the left, consider that to be a normal individual. And you can see that there is uptake in the heart, very little uptake in the mediastinum. And one can then make a cardiac-to-mediastinal ratio of MIBG uptake. Those of you with sharp eyes will notice that actually is not a normal individual; that is an individual with multiple system atrophy. And we'll come back to that in future slides. Over on the right is an individual with Parkinson's disease. And you can see that there is markedly less uptake in the heart. And so the heart-to-mediastinal ratio of MIBG uptake would be markedly reduced.
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Autonomic Dysfunction in Parkinson’s Disease

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