What is the relationship between postural hypotension (orthostatic hypotension) and neurodegenerative disorders?

From the Guidelines

Postural hypotension is a significant complication in neurodegenerative disorders, and its management should prioritize non-pharmacological strategies, followed by pharmacological interventions, with midodrine and droxidopa being the most effective treatments, as evidenced by the most recent study 1.

Non-Pharmacological Interventions

Non-pharmacological measures are the first line of treatment for postural hypotension, including:

• Gradual position changes
• Increased fluid intake (2-3 liters daily)
• Salt supplementation (up to 10g daily)
• Compression stockings
• Elevating the head of the bed by 30 degrees at night These measures aim to minimize postural symptoms rather than restore normotension, as stated in the 2022 study 1.

Pharmacological Interventions

If non-pharmacological measures are insufficient, pharmacological treatment should be considered. The most effective treatments for postural hypotension are:

• Midodrine, starting at 2.5mg three times daily (maximum 10mg three times daily, with last dose before 6pm to avoid supine hypertension)
• Droxidopa (100-600mg three times daily), which may be particularly useful in Parkinson's disease and multiple system atrophy These medications work through different mechanisms, with midodrine directly increasing vascular tone and droxidopa converting to norepinephrine to increase blood pressure, as described in the 2017 study 1.

Pathophysiology

The underlying pathophysiology in neurodegenerative disorders involves autonomic dysfunction affecting sympathetic vasoconstrictor pathways, which normally compensate for blood pooling during positional changes, leading to inadequate blood pressure maintenance when standing, as explained in the 2011 study 1.

Key Considerations

When managing postural hypotension, it is essential to consider the following:

• Physical activity and exercise should be encouraged to avoid deconditioning, which can exacerbate orthostatic intolerance
• Volume repletion with fluids and salt is critical
• Supine blood pressure tends to be much higher in these patients, often requiring treatment of blood pressure at bedtime with shorter-acting drugs, as mentioned in the 2022 study 1

From the Research

Relationship between Postural Hypotension and Neurodegenerative Disorders

• Postural hypotension, also known as orthostatic hypotension, is a condition characterized by a drop in blood pressure when standing up, which can lead to symptoms such as dizziness, lightheadedness, and fainting 2.
• Neurodegenerative disorders, such as Parkinson's disease, multiple system atrophy, and pure autonomic failure, are often associated with orthostatic hypotension, which can be a debilitating and disabling problem for patients 2.
• The relationship between postural hypotension and neurodegenerative disorders is complex, and the exact mechanisms are not fully understood, but it is thought that the loss of sympathetic nerves in the heart and other organs may contribute to the development of orthostatic hypotension 3.

Epidemiology and Diagnosis

• Orthostatic hypotension is a common problem in the elderly, with a significant number of hospital admissions attributed to this condition, particularly in patients over 75 years of age 2.
• The diagnosis of orthostatic hypotension is typically made based on a sustained fall in blood pressure on standing, which can be measured using a variety of methods, including tilt table testing and ambulatory blood pressure monitoring 2.

Management and Treatment

• The management of orthostatic hypotension typically involves a combination of non-pharmacological and pharmacological interventions, including increasing fluid and salt intake, wearing compression garments, and taking medications such as fludrocortisone 4, 5.
• Non-pharmacological interventions, such as physical counter-maneuvers, aerobic or resistance exercises, and sleeping with the head tilted up, may also be effective in treating orthostatic hypotension, particularly in patients with mild to moderate symptoms 6.
• The choice of treatment will depend on the underlying cause of the orthostatic hypotension, as well as the severity of symptoms and the presence of any underlying medical conditions 2.

Pathophysiology

• The pathophysiology of orthostatic hypotension in neurodegenerative disorders is thought to involve the loss of sympathetic nerves in the heart and other organs, which can lead to a decrease in norepinephrine release and a subsequent drop in blood pressure on standing 3.
• Decreased vesicular uptake of catecholamines, such as dopamine and norepinephrine, into storage vesicles within sympathetic neurons may also contribute to the development of orthostatic hypotension in patients with Lewy body diseases, such as Parkinson's disease and pure autonomic failure 3.