Overview
Autonomic neuropathy is damage to the autonomic nerves, the part of the nervous system that controls functions we do not think about, such as heart rate, blood pressure, digestion, bladder control, sexual function, sweating and temperature regulation.
The most common cause is long-standing diabetes, but it can also result from Parkinson's disease, amyloidosis, autoimmune conditions, some infections, alcohol and certain cancer treatments. Symptoms depend on which nerves are affected and include dizziness or fainting on standing, a fast resting heart rate, feeling full quickly, vomiting, constipation or diarrhoea, bladder problems, erectile dysfunction and abnormal sweating. There is often no cure, but treating the cause and managing symptoms can greatly improve quality of life.
When to get urgent help
Seek emergency care for fainting with injury, chest pain, severe persistent vomiting, inability to pass urine, or signs of severe low blood sugar.
Causes and risk factors
- Diabetes: the most common cause, especially with long duration and poor control
- Neurodegenerative diseases: Parkinson's disease, multiple system atrophy, Lewy body dementia, pure autonomic failure
- Amyloidosis: AL and hereditary transthyretin amyloidosis
- Autoimmune conditions: autoimmune autonomic ganglionopathy, Sjögren's syndrome, lupus, Guillain-Barré syndrome
- Infections: HIV, Lyme disease, leprosy, botulism, Chagas disease
- Alcohol misuse
- Medicines: some chemotherapy (vincristine, cisplatin), amiodarone
- Cancer-related (paraneoplastic) syndromes
- Inherited neuropathies
- Vitamin B12 deficiency
How it develops (pathophysiology)
Normal autonomic function
The autonomic nervous system has two main branches that work in balance:
- The sympathetic nervous system ("fight or flight") tightens blood vessels, raises heart rate and blood pressure, and stimulates sweating
- The parasympathetic nervous system ("rest and digest"), mainly via the vagus nerve, slows the heart and stimulates digestion, bladder emptying and sexual arousal
When we stand up, gravity pools about half a litre of blood in the legs. Pressure sensors (baroreceptors) in the neck and chest detect the drop in blood pressure and trigger sympathetic nerves to tighten blood vessels and speed up the heart, keeping blood pressure stable within seconds.
What goes wrong
Autonomic nerves are often small, thin fibres with little or no insulating myelin, which makes them vulnerable to damage:
- In diabetes, high blood sugar damages nerves through several mechanisms: accumulation of sorbitol and advanced glycation end products, oxidative stress, inflammation, and damage to the tiny blood vessels supplying nerves (microangiopathy). The longest nerves are affected first; the vagus nerve, one of the longest, is often affected early, so parasympathetic loss (fast resting heart rate) may appear before sympathetic loss.
- In neurodegenerative diseases, abnormal alpha-synuclein protein accumulates in autonomic neurons or brain regions controlling them.
- In amyloidosis, protein deposits infiltrate and damage nerves.
- In autoimmune forms, antibodies attack receptors at autonomic ganglia, where nerve signals are relayed.
Why the symptoms happen
- Dizziness or fainting on standing (orthostatic hypotension): sympathetic nerves fail to tighten blood vessels, so blood pools in the legs and blood pressure falls.
- Fast resting heart rate and fixed heart rate: loss of vagal slowing.
- Silent heart attacks: damage to pain-sensing nerves from the heart.
- Feeling full quickly, bloating, nausea and vomiting (gastroparesis): vagus nerve damage slows stomach emptying.
- Constipation or diarrhoea: disrupted gut motility.
- Bladder problems: weak bladder contraction causes incomplete emptying and infections.
- Erectile dysfunction and vaginal dryness: reduced nerve control of blood flow.
- Reduced or excessive sweating: loss of sweat gland nerve supply, with compensatory sweating elsewhere.
- Reduced awareness of low blood sugar: blunted adrenaline response in people with diabetes.
How treatment acts on the mechanism
Improving blood sugar control slows further nerve damage in diabetes. Midodrine tightens blood vessels, and fludrocortisone expands blood volume, both raising standing blood pressure. Droxidopa is converted to noradrenaline. Prokinetic medicines speed stomach emptying. Lifestyle measures such as increasing fluid and salt intake, compression garments and rising slowly support blood pressure.
Types
- Diabetic autonomic neuropathy, including cardiovascular autonomic neuropathy and gastroparesis
- Autonomic failure in neurodegenerative disease
- Autoimmune autonomic ganglionopathy
- Small fibre neuropathy with autonomic features
- Postural orthostatic tachycardia syndrome (PoTS) is a related condition
Signs and symptoms
- Dizziness, light-headedness or fainting when standing
- Fast heartbeat at rest
- Exercise intolerance
- Feeling full quickly, nausea, vomiting, bloating
- Constipation, diarrhoea or faecal incontinence
- Difficulty emptying the bladder, frequent urinary infections
- Erectile dysfunction, vaginal dryness
- Reduced sweating on the feet and legs, or excessive sweating of the upper body
- Heat intolerance
- Reduced awareness of low blood sugar
- Blurred vision in bright or dim light (pupil changes)
How it is diagnosed
- Lying and standing blood pressure and heart rate
- Autonomic function tests: heart rate response to deep breathing and the Valsalva manoeuvre, tilt-table testing
- Gastric emptying study
- Bladder ultrasound to measure residual urine
- Sweat tests
- Blood tests: glucose, HbA1c, B12, amyloid tests, antibodies
- Nerve conduction studies and skin biopsy for small fibre neuropathy
Possible complications
- Falls and injuries
- Silent heart attacks and sudden cardiac death
- Malnutrition and poor diabetes control from gastroparesis
- Urinary infections and kidney damage
- Heat stroke from reduced sweating
- Severe low blood sugar episodes
Goals of treatment
Treatment aims to treat the underlying cause, relieve symptoms, prevent falls and complications, and improve quality of life.
Medicines
- Orthostatic hypotension: midodrine, fludrocortisone, droxidopa, pyridostigmine
- Gastroparesis: metoclopramide or domperidone (short term, with safety monitoring), erythromycin
- Constipation or diarrhoea: laxatives or anti-diarrhoeal medicines
- Bladder: medicines to help emptying, or intermittent catheterisation
- Erectile dysfunction: PDE5 inhibitors such as sildenafil, if safe
- Treatment of the cause: diabetes control, amyloidosis therapies, immunotherapy for autoimmune forms
Other treatments
- Increase fluid (2 to 3 litres a day) and salt intake if advised
- Wear compression stockings or abdominal binders
- Stand up slowly and sit if dizzy
- Raise the head of the bed
- Eat small, frequent, low-fat, low-fibre meals for gastroparesis
- Avoid hot environments and heavy meals
- Physiotherapy and exercise adapted to tolerance
Living with it and prevention
- Keep blood sugar, blood pressure and cholesterol well controlled in diabetes
- Avoid excess alcohol
- Have regular diabetes reviews, including checks for nerve damage
- Review medicines that worsen low blood pressure
Monitoring and follow-up
Regular reviews check blood pressure (lying and standing), heart rate, weight, bladder function and diabetes control. People with cardiovascular autonomic neuropathy may need heart assessment.
Outlook
Autonomic neuropathy is often long-term. Symptoms can usually be managed, and treating the cause, especially in diabetes, may slow progression.
Special considerations
- People with diabetes: screening is recommended, especially with long-standing diabetes
- Older adults: higher fall risk
- Pregnancy: gastroparesis and blood pressure changes need careful management
