What are the diagnostic criteria and treatment options for autonomic neuropathy?

How to Tell if You Have Autonomic Neuropathy

Autonomic neuropathy is diagnosed through a combination of specific symptom assessment and cardiovascular autonomic reflex testing (CARTs), with definite diagnosis requiring at least two abnormal cardiovagal test results. 1, 2

Clinical Symptoms to Assess

Cardiovascular Manifestations

• Resting tachycardia >100 bpm is often the earliest sign 2, 3
• Orthostatic hypotension: A fall in systolic blood pressure >20 mmHg or diastolic >10 mmHg upon standing without appropriate heart rate increase 1, 2
• Orthostatic dizziness or syncope (fainting) 3
• Exercise intolerance 4

Gastrointestinal Symptoms

• Gastroparesis (delayed stomach emptying) causing erratic blood sugar control, early satiety, nausea, vomiting 1, 4
• Constipation alternating with diarrhea 4
• Nocturnal diarrhea 5

Genitourinary Symptoms

• In men: Erectile dysfunction and/or retrograde ejaculation 1, 4
• In women: Decreased sexual desire, pain during intercourse, decreased arousal, inadequate lubrication 1, 2
• Bladder dysfunction: Urinary incontinence, nocturia, frequent urination, urgency, weak stream 1, 2
• Recurrent urinary tract infections 4

Sudomotor (Sweating) Abnormalities

• Dry, cracked skin in the extremities 3
• Loss of sweating in feet 2
• Compensatory hyperhidrosis (excessive sweating) in upper body 1
• Warm skin due to increased peripheral blood flow 2

Diagnostic Testing

First-Line: Cardiovascular Autonomic Reflex Tests (CARTs)

These are the gold standard for diagnosis 2, 6:

1. Heart rate variability with deep breathing (cardiovagal function) - the earliest detectable abnormality, even before symptoms 2, 4
2. Valsalva maneuver (cardiovagal and sympathetic function) 4
3. Postural blood pressure testing (sympathetic adrenergic function) 4

Diagnostic criteria 2:

• Early/possible autonomic neuropathy: One abnormal cardiovagal test
• Definite/confirmed autonomic neuropathy: At least two abnormal cardiovagal tests
• Severe/advanced autonomic neuropathy: Orthostatic hypotension plus abnormal heart rate tests

Additional Specialized Testing

• Ambulatory blood pressure monitoring for early identification 6
• Scintigraphy and electrogastrography for gastrointestinal neuropathy 1
• Bladder ultrasound to measure residual urine volume for bladder dysfunction 1
• Sympathetic skin response and heart rate variability if autonomic neuropathy suspected 1
• Skin biopsy showing reduced intraepidermal nerve density (only helpful in selected cases with clinical-physiological correlation) 6

Initial Laboratory Workup

Rule out other causes before confirming autonomic neuropathy 6:

• Fasting glucose or oral glucose tolerance test
• Thyroid function tests
• Kidney function tests
• Vitamin B12 level
• Serum and urine protein electrophoresis with immunofixation

When to Suspect Autonomic Neuropathy

High-Risk Populations

• Diabetic patients: Screen at diagnosis for type 2 diabetes and 5 years after diagnosis of type 1 diabetes 3
• Patients with other microvascular complications (kidney disease, diabetic peripheral neuropathy) 2
• Long-standing diabetes (prevalence up to 65%) 2
• Approximately 20% of asymptomatic diabetic individuals have abnormal cardiovascular autonomic function 4

Red Flags Requiring Immediate Evaluation

• Recurrent urinary tract infections or pyelonephritis 1, 4
• Palpable bladder 1
• Erratic glucose control suggesting gastroparesis 4
• Symptoms of orthostatic hypotension 1

Critical Clinical Pearls

Up to 50% of diabetic peripheral neuropathy may be asymptomatic, requiring proactive screening rather than waiting for symptoms 3. Autonomic symptoms often appear alongside sensory and motor deficits in generalized polyneuropathy 2.

Cardiovascular autonomic neuropathy is independently associated with increased mortality risk, making early detection crucial 1, 3. The presence of CAN doubles the relative risk of silent myocardial ischemia and mortality 4.

Autonomic neuropathy is a diagnosis of exclusion - other causes must be ruled out including alcohol toxicity, vitamin B12 deficiency, hypothyroidism, renal disease, chemotherapy, and amyloidosis 3, 7, 8.

Electrophysiological testing (EMG) or neurologist referral is rarely needed except when clinical features are atypical or diagnosis is unclear 1. Standard neurophysiological techniques may be normal in small fiber neuropathies 1.