Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by an abnormal increase in heart rate upon standing, often accompanied by lightheadedness, fatigue, and brain fog. This condition falls under dysautonomia, involving a malfunction of the autonomic nervous system, which controls involuntary functions like heart rate and blood pressure. Neuropathic POTS is a recognized subtype, distinguished by damage to the peripheral nerves. Recognizing this subtype is important because the specific mechanism dictates a tailored approach to diagnosis and management.
The Defining Mechanism: Autonomic Nerve Dysfunction
Neuropathic POTS arises from partial denervation, or loss of nerve supply, primarily affecting the small-fiber peripheral nerves in the lower extremities and abdomen. These small-fiber nerves are part of the sympathetic nervous system and regulate the constriction of blood vessels. When a healthy individual stands, these nerves release norepinephrine, signaling blood vessels to tighten and preventing blood from pooling in the lower body.
In Neuropathic POTS, nerve damage impairs norepinephrine release, resulting in poor vasoconstriction in the legs. This failure allows significant blood accumulation in the lower limbs and splanchnic (abdominal) circulation, known as venous pooling. The pooling reduces the blood returning to the heart, decreasing the stroke volume. The body compensates for this drop in central blood volume by excessively increasing the heart rate, leading to the sustained tachycardia that defines POTS. This length-dependent autonomic neuropathy is the core physiological difference separating this subtype from others.
Identifying Clinical Markers
The nerve damage underlying Neuropathic POTS manifests in distinct physical and sensory symptoms, not just cardiovascular changes. Patients often experience signs of sensory small fiber neuropathy, including burning, tingling, or electric-shock-like pain, particularly in the feet and lower legs.
Another clinical marker is the loss of sweating, or anhidrosis, in the lower limbs, as the small fibers also control the sweat glands. When standing, many patients develop dependent acrocyanosis, where the feet and lower legs appear reddish-purple or mottled. This discoloration is a visible sign of excessive blood pooling and stagnant circulation caused by failed vasoconstriction.
Diagnostic Confirmation
The initial step in diagnosis is confirming the presence of POTS, typically done through a Tilt Table Test. This test measures heart rate and blood pressure response as the patient is passively tilted upright. A sustained increase in heart rate of at least 30 beats per minute within the first ten minutes of standing, without a significant drop in blood pressure, meets the criteria for POTS in adults.
To confirm the specific neuropathic subtype, specialized testing is required to demonstrate underlying small fiber neuropathy (SFN). A common method is a skin punch biopsy, often taken from the lower leg. The sample is analyzed to measure the intraepidermal nerve fiber density (IENFD); a reduced density indicates nerve damage consistent with SFN.
Another useful test is the quantitative sudomotor axon reflex testing (QSART), which assesses the function of small autonomic nerves regulating sweating. QSART measures the volume of sweat produced in response to a chemical stimulant. Reduced sweat output, especially in a length-dependent pattern, provides physiological evidence of small fiber autonomic dysfunction. Neuropathic POTS is established when a positive Tilt Table Test is paired with objective evidence of SFN from these specialized tests.
Targeted Management Strategies
Management for Neuropathic POTS focuses on mitigating the effects of blood pooling and compensating for the volume deficit. Non-pharmacological strategies include significantly increasing fluid and salt intake to expand blood volume.
Specialized compression garments, such as high-waisted abdominal binders and compression stockings (20–30 mm Hg of pressure), are recommended. This external pressure mechanically limits the venous pooling resulting from poor nerve signaling. Exercise protocols focus on recumbent activities like rowing or swimming, which improve cardiovascular conditioning without relying on upright posture. Strength training builds leg muscle mass, which acts as a “muscle pump” to push blood back toward the core.
Pharmacological treatments promote vasoconstriction and manage heart rate. Midodrine, an alpha-1 adrenergic agonist, is frequently prescribed because it acts directly on the blood vessels to cause tightening. Pyridostigmine increases the availability of the neurotransmitter acetylcholine, enhancing nerve signaling and reducing upright tachycardia. If an underlying autoimmune process is suspected, immune-modulating therapies may be considered to address the root of the neuropathy.