Science Sunday: Baroreflex Dysfunction and Orthostatic Hypotension in Parkinson’s

“Winning comes down to who can execute under pressure.” Billie Jean King

“No pressure, no diamonds.” Thomas Carlyle

Scenario #1: You’re lying on the floor for a stretch in a physical therapy session. You rise to your feet, and the world starts spinning suddenly. You feel dizzy and disoriented, and the room takes a few minutes to stop its dizzying dance. This is a classic case of orthostatic hypotension.

Scenario #2: You are celebrating your grandchild’s birthday with family and have just eaten a big meal. All of a sudden, you feel dizzy and light-headed and like you are going to faint.

Scenario #3: You are at your Movement Disorder Neurologist’s office, and they’re measuring your blood pressure. They do this while you sit and then again when you stand up. Suppose the top number (systolic blood pressure) drops by 20 millimeters of mercury (mm Hg) within 2 to 5 minutes of standing. In that case, it’s a sign of orthostatic hypotension.

These are three examples of hypotension, a sudden fall in blood pressure lower than usual. This blog post briefly overviews orthostatic hypotension and baroreflex dysfunction.

“The longer I live, the less future there is to worry about.” Ashleigh Brilliant

Autonomic Nervous System (ANS): The ANS innervates all our body organs, including the cardiovascular system. Its role in the vasculature is to regulate blood flow and redirect vascular flow where needed. The ANS gives this instantaneous response through baroreflexes.

Baroreflexes allow the circulatory system to adapt to varying conditions in daily life, maintaining blood pressure, heart rate, and blood volume within a well-described physiological range.
•Baroreceptors in our major arteries and veins constantly signal the brain stem through the vagus and glossopharyngeal nerves, and they are activated when blood pressure, blood volume, or both rise.
•To counter this rise, baroreceptors cause reflex inhibition of skeletal muscle and kidney blood vessels, which causes vasodilation.
•At the same time, nervous impulses increase the parasympathetic-nerve response in the sinoatrial node, which slows the heart rate.
•When one changes to a standing position, baroreceptors are unloaded, promoting vasoconstriction and tachycardia (rapid increase in heart rate) to help with the fall in blood pressure that would otherwise occur.
• Intriguingly, baroreceptors in the carotid sinuses and aortic arch sense blood pressure changes, and cardiopulmonary baroreceptors in the thoracic veins and the heart sense changes in blood volume.

“If you don’t know your blood pressure, it’s like not knowing the value of your company.” Mehmet Oz

Efferent Baroreflex Failure: Many diseases disrupt efferent baroreflexes, including Parkinson’s. The result is the impaired release of norepinephrine at the neurovascular junction. This results in insufficient vasoconstriction on standing or exertion, which results in orthostatic hypotension. Symptoms include lightheadedness, dizziness, visual blurring, and even syncope (a loss of consciousness for a short period of time). The damage to baroreflex efferent neurons is most often caused by diabetes mellitus and then, secondly, by synucleinopathies (accumulation of misfolded alpha-synuclein) in nerve tissue.

“Trust is like blood pressure. It’s silent, vital to good health, and if abused it can be deadly.” Frank K. Sonnenberg

Dealing/Managing Orthostatic Hypotension in Parkinson’s: Symptoms of ANS dysfunctions are challenging and definitely reduce the quality of life in patients with Parkinson’s. Effective management relies on patient education and, importantly, proper recognition of the ANS dysfunction (in this case, orthostatic hypotension) and appropriate non-drug and drug therapies.

NOTE: Remember, I am NOT a physician, and any use of the strategies and information provided below must be carefully discussed with your Neurologist and primary care physicians.

For mild orthostatic hypotension, sit or lie back down immediately after feeling lightheaded upon standing. Your symptoms may rapidly improve.

Self-care is important to live successfully with orthostatic hypotension. Here is what the Mayo Clinic suggests (click here for the full details): wearing waist-high compression stockings; getting plenty of fluids; avoiding alcohol; increasing salt in the diet (do not overdo this because too much salt will lead to other problems); eating small meals; exercising (try to avoid hot and humid conditions); moving and stretching in certain ways; getting up slowly; raising the head of the bed.

In more severe cases of orthostatic hypotension, your Neurologist may prescribe drugs to counter the effect of hypotension. Several medications, including fludrocortisone, midodrine, and droxidopa, may help treat orthostatic hypotension in Parkinson’s. However, long-term use of fludrocortisone in high doses increases the risk of heart failure and renal fibrosis, which could be fatal. The alpha-adrenergic agonist midodrine and the norepinephrine precursor droxidopa are relatively safe and short-acting. This is a difficult clinical treatment because these conditions of orthostatic (low blood pressure that happens when standing after sitting or lying down) hypotension and supine (lying horizontally with the face and torso facing up) hypertension can co-exist, and treatment of one usually worsens the other.

Many known drugs can worsen orthostatic hypotension. Unfortunately, antiparkinsonian drugs (levodopa, dopamine agonists, monoamine oxidase inhibitors) are on the list. Also included are several diuretics, adrenergic blockers, alpha₂-adrenergic agonists, nitric oxide-mediated vasodilators, renin-angiotensin-aldosterone system blockers, calcium-channel blockers, dopamine antagonists, tricyclic antidepressants, and selective serotonin receptor reuptake inhibitors. Thus, further reinforcing my comment above, it is important to carefully work with your physicians to better focus on controlling your symptoms of orthostatic hypotension.

“When a train goes through a tunnel and it gets dark, you don’t throw away the ticket and jump off. You sit still and trust the engineer.” Corrie Ten Boom

Conclusions: ANS dysfunctions are important non-motor issues of Parkinson’s. ANS disturbances in Parkinson’s are more than just orthostatic hypotension. Other ANS dysfunctions include gastrointestinal issues, urinary complications, sexual dysfunction, tear anomalies, and thermoregulatory disturbances. The cause is usually thought to be related to alpha-synuclein accumulation, but it has not yet been proven for all ANS disturbances.

Your continued education and knowledge of these ANS-related problems can be taken to your neurologist and carefully studied. We all know that Parkinson’s attacks us all differently, but ANS dysfunctions are one of the most common non-motor occurrences. Please stay healthy, keep moving, do not stop learning, and always stay attuned to what is happening to you symptom-wise.

“Worrying is carrying tomorrow’s load with today’s strength- carrying two days at once. It is moving into tomorrow ahead of time. Worrying doesn’t empty tomorrow of its sorrow, it empties today of its strength.” Corrie Ten Boom

References:
Palma, Jose‐Alberto, and Horacio Kaufmann. “Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.” Movement Disorders 33, no. 3 (2018): 372-390.

Chen, Zhichun, Guanglu Li, and Jun Liu. “Autonomic dysfunction in Parkinson’s disease: Implications for pathophysiology, diagnosis, and treatment.” Neurobiology of Disease 134 (2020): 104700.

Kaufmann, Horacio, Lucy Norcliffe-Kaufmann, and Jose-Alberto Palma. “Baroreflex dysfunction.” New England Journal of Medicine 382, no. 2 (2020): 163-178.

Zhu, Shuzhen, Hualing Li, Xiaoyan Xu, Yuqi Luo, Bin Deng, Xingfang Guo, Yang Guo, Wucheng Yang, Xiaobo Wei, and Qing Wang. “The pathogenesis and treatment of cardiovascular autonomic dysfunction in Parkinson’s disease: what we know and where to go.” Aging and disease 12, no. 7 (2021): 1675.

Milazzo, Valeria, Cristina Di Stefano, Fabrizio Vallelonga, Gabriele Sobrero, Maurizio Zibetti, Alberto Romagnolo, Aristide Merola et al. “Reverse blood pressure dipping as marker of dysautonomia in Parkinson disease.” Parkinsonism & Related Disorders 56 (2018): 82-87.

Senard, J. M., S. Rai, M. Lapeyre-Mestre, C. Brefel, O. Rascol, A. Rascol, and J. L. Montastruc. “Prevalence of orthostatic hypotension in Parkinson’s disease.” Journal of Neurology, Neurosurgery & Psychiatry 63, no. 5 (1997): 584-589.

Goldstein, D. S., C. S. Holmes, R. Dendi, S. R. Bruce, and S-T. Li. “Orthostatic hypotension from sympathetic denervation in Parkinson’s disease.” Neurology 58, no. 8 (2002): 1247-1255.