Definition and Overview
Parkinson's disease is a neurodegenerative disease characterized by loss of dopaminergic neurons and accumulation of Lewy bodies in the substantia nigra. Pathological changes in Parkinson's disease are not limited to the substantia nigra, which causes motor symptoms, but also involve a wide range of neural structures, including the autonomic nervous system.
Approximately 70-80% of Parkinson's disease patients exhibit various autonomic dysfunction, which accounts for an important part of non-motor symptoms (NMS). Autonomic symptoms have a significant impact on quality of life independently of motor symptoms, and some function as prodromal symptoms that appear before motor symptoms.
Mechanism of occurrence
According to Braak staging, Lewy body pathology in Parkinson's disease first begins in the lower part of the brainstem and peripheral autonomic nerves (especially the enteric nervous system and cardiac sympathetic nerves) and spreads upward. This explains that autonomic symptoms such as constipation and cardiac sympathetic denervation may appear before motor symptoms (substantia nigra involvement).
Peripheral autonomic nerve involvement includes cardiac sympathetic denervation and Lewy body involvement in the enteric nervous system. Centrally, damage to the hypothalamus, brainstem autonomic nuclei (nucleus tractus solitarius, dorsal vagal nucleus, etc.), and spinal cord intermediolateral cell column contributes to autonomic dysfunction.
Parkinson's disease treatments (especially dopamine agonists and levodopa) can also cause or worsen autonomic symptoms (orthostatic hypotension, nausea, etc.).
Orthostatic hypotension
Orthostatic hypotension is reported in approximately 30-58% of Parkinson's disease patients. When standing, the sympathetic vasoconstrictor response is impaired and blood pressure is not properly maintained. Symptoms include dizziness, headache, blurred vision, presyncope, and fainting.
Orthostatic hypotension increases the risk of falls and fractures, and is also associated with decreased cognitive function and increased mortality. Parkinson's disease medications, especially dopamine agonists, can worsen orthostatic hypotension, so medication adjustment is necessary.
For treatment, first attempt non-pharmacological methods (sufficient fluid/salt intake, compression stockings, sleep with head elevated), and use fludrocortisone, midodrine, and droxidopa when necessary.
Gastrointestinal autonomic dysfunction
Constipation is one of the most common non-motor symptoms in Parkinson's disease, occurring in approximately 80% of patients. Intestinal motility is reduced due to Lewy body invasion of the enteric nervous system. Constipation is recognized as a prodromal symptom that appears years to decades before motor symptoms, and longitudinal studies have shown that men with constipation have a higher risk of developing Parkinson's disease.
Swallowing disorders (dysphagia) occur due to dysfunction of the esophagus and pharynx and are a risk factor for aspiration pneumonia. Saliva hypersecretion (sialorrhea) is a phenomenon in which saliva accumulates due to a decrease in the frequency of swallowing rather than an actual increase in saliva production.
bladder dysfunction
Bladder dysfunction is reported in approximately 70% of Parkinson's disease patients. Overactive bladder is the most common, causing frequent urination, nocturia, and urge incontinence. This is because in Parkinson's disease, the bladder detrusor muscle becomes hyperactive due to the loss of the dopaminergic inhibition mechanism. In some patients, difficulty urinating, residual urine, and urinary tract infections occur repeatedly due to decreased detrusor muscle contraction.
Sweating and temperature regulation difficulties
Abnormal sweating is reported in approximately 64% of Parkinson's disease patients. Symptoms vary and may include generalized or localized hyperhidrosis, night sweats, or anhidrosis. Rapid sweating may occur at peak levodopa doses.
Cardiac autonomic and MIBG scans
In Parkinson's disease, cardiac sympathetic denervation can be confirmed by MIBG (123I-metaiodobenzylguanidine) scan. MIBG is an analogue of norepinephrine and is absorbed into cardiac sympathetic nerve endings. While MIBG uptake is reduced in Parkinson's disease patients, cardiac MIBG uptake is relatively preserved in multiple system atrophy (MSA). This finding is used as an aid in the differential diagnosis of the two diseases.
In heart rate variability (HRV) tests, patients with Parkinson's disease show a decrease in overall HRV, with both the high frequency (HF) component (parasympathetic index) and low frequency (LF) component (sympathetic index) decreasing.
Diagnosis and Evaluation
SCOPA-AUT (Scales for Outcomes in Parkinson's disease—Autonomic) is a standard survey tool that quantitatively assesses autonomic symptoms in Parkinson's disease. An objective evaluation is performed using a battery of autonomic function tests, including heart rate variability test, standing tilt test, Valsalva maneuver, and sweating function test (QSART).
treatment
Autonomic symptoms are managed individually for each symptom. Non-pharmacological approaches and drug treatment are combined for each of orthostatic hypotension, bladder dysfunction, constipation, and sweating abnormalities. Because medications used to treat Parkinson's motor symptoms may affect autonomic symptoms, the overall medication plan should be carefully adjusted.