What features are associated with autonomic nervous system (ANS) dysfunction?

From the Guidelines

Autonomic nervous system (ANS) dysfunction is associated with a range of features, including orthostatic hypotension, tachycardia or bradycardia, anhidrosis or hyperhidrosis, temperature dysregulation, and gastrointestinal symptoms, as well as exercise intolerance, fatigue, dizziness, syncope, and blurred vision, as reported in the most recent study 1.

Key Features of ANS Dysfunction

• Orthostatic hypotension, defined as a drop in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg within 3 minutes of standing 1
• Tachycardia or bradycardia, with resting tachycardia (>100 bpm) being a common finding in cardiac autonomic neuropathy (CAN) 1
• Anhidrosis (reduced sweating) or hyperhidrosis (excessive sweating), which can be associated with temperature dysregulation 1
• Gastrointestinal symptoms, such as early satiety, nausea, and delayed gastric emptying, which can be debilitating and affect quality of life 1
• Exercise intolerance, fatigue, dizziness, syncope (fainting), and blurred vision, which can be caused by orthostatic intolerance and CAN 1

Pathophysiology and Classification

The autonomic nervous system regulates involuntary bodily functions through its sympathetic and parasympathetic branches. When this system malfunctions, the body loses its ability to maintain homeostasis and properly respond to environmental changes. The dysfunction can be primary (as in pure autonomic failure) or secondary to conditions like diabetes, Parkinson's disease, or certain medications. Classification of orthostatic hypotension includes initial OH, classical OH, delayed OH, and neurogenic OH, each with distinct pathophysiological mechanisms and clinical manifestations 1.

Clinical Implications

ANS dysfunction can have significant clinical implications, including increased risk of mortality, morbidity, and decreased quality of life. Early recognition and management of ANS dysfunction are crucial to prevent long-term complications and improve patient outcomes. Comprehensive management strategies targeting specific symptoms and underlying conditions are necessary to alleviate symptoms and improve quality of life 1.

From the FDA Drug Label

Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias) 2 Neuroleptic Malignant Syndrome Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported This potentially fatal syndrome is comprised of the symptom complex of hyperthermia, muscular rigidity, altered consciousness, and autonomic instability (see WARNINGS) 2 The features associated with autonomic nervous system (ANS) dysfunction are:

• Irregular pulse or blood pressure
• Tachycardia
• Diaphoresis
• Cardiac arrhythmias These features are part of the clinical manifestations of Neuroleptic Malignant Syndrome (NMS) 2 2

From the Research

Features of Autonomic Nervous System (ANS) Dysfunction

The features associated with ANS dysfunction can be categorized into several key areas, including:

• Orthostatic hypotension (OH), which is a blood pressure fall when standing from the supine to the erect position 3
• Orthostatic intolerance, including orthostatic hypotension or tachycardia 4
• Sweating abnormalities, such as increased or decreased sweating 4
• Genitourinary and intestinal dysfunction 5
• Sweating disorders 5
• Neurogenic supine hypertension (nSH), characterized by elevated blood pressure when supine 6
• Neurogenic orthostatic hypotension (nOH), resulting in a sustained blood pressure drop upon standing 6
• Symptoms such as lightheadedness, orthostatic dizziness, presyncope, and syncope 6

Pathophysiology of ANS Dysfunction

ANS dysfunction may result from diseases that affect primarily either the central nervous system or the peripheral autonomic nervous system 7. The pathophysiology of ANS dysfunction can involve:

• Degeneration of the intermediolateral cell columns (progressive autonomic failure) 7
• Disease or damage to descending pathways that synapse on the intermediolateral column cells 7
• Damage to the peripheral autonomic nervous system, including small myelinated and unmyelinated fibers 7
• Acute demyelination of the sympathetic and parasympathetic nerves in the Guillain-Barré syndrome 7

Clinical Characteristics of ANS Dysfunction

The clinical characteristics of ANS dysfunction can vary depending on the underlying condition, but may include:

• Postural blood pressure dysregulation 6
• Elevated blood pressure when supine 6
• Sustained blood pressure drop upon standing 6
• Symptoms such as lightheadedness, orthostatic dizziness, presyncope, and syncope 6
• Genitourinary and intestinal dysfunction 5
• Sweating disorders 5