What are the clinical features of autonomic neuropathy?

Clinical Features of Autonomic Neuropathy

Autonomic neuropathy presents with a diverse range of clinical manifestations affecting multiple organ systems, primarily involving cardiovascular, gastrointestinal, urogenital, and sudomotor functions. 1, 2

Cardiovascular Manifestations

• Resting tachycardia (>100 bpm) is often an early sign of cardiovascular autonomic neuropathy (CAN) 1
• Orthostatic hypotension (a fall in systolic or diastolic blood pressure by >20 mmHg or >10 mmHg, respectively, upon standing without appropriate heart rate increase) is a hallmark feature of advanced CAN 1, 2
• Decreased heart rate variability with deep breathing is often the earliest detectable abnormality in CAN, even before symptoms appear 1, 2
• Exercise intolerance due to impaired cardiovascular response to exertion 1, 3
• Non-dipping or reverse dipping blood pressure patterns during sleep 1
• QT interval prolongation, which increases risk of arrhythmias 1
• Silent myocardial ischemia due to impaired pain perception 1

Gastrointestinal Manifestations

• Early satiety, nausea, and vomiting due to gastroparesis 2, 4
• Alternating diarrhea and constipation due to abnormal gut motility 4
• Postprandial hypotension occurring after meals 1
• Fecal incontinence due to impaired rectal sensation and sphincter control 5

Urogenital Manifestations

• Erectile dysfunction in males is a common early manifestation 1, 4
• Female sexual dysfunction including decreased sexual desire, increased pain during intercourse, decreased arousal, and inadequate lubrication 1
• Bladder dysfunction presenting as urinary incontinence, nocturia, frequent urination, urination urgency, and weak urinary stream 1, 4
• Urinary retention and recurrent urinary tract infections 1, 5

Sudomotor Dysfunction

• Abnormal sweating patterns, including hyperhidrosis or anhidrosis 2, 4
• Dry, cracked skin in extremities due to decreased sweating 2, 3
• Heat intolerance due to impaired thermoregulation 4, 5

Peripheral Vascular Manifestations

• Increased peripheral blood flow resulting in warm skin 1
• Increased arteriovenous shunting with swollen veins 1
• Increased venous pressure leading to leg and foot edema 1
• Loss of protective cutaneous vasomotor reflexes 1

Clinical Progression and Staging

• Early/possible CAN: One abnormal cardiovagal test result 1
• Definite/confirmed CAN: At least two abnormal cardiovagal test results 1
• Severe/advanced CAN: Presence of orthostatic hypotension in addition to abnormal heart rate test results 1
• Progressive stages of CAN are associated with increasingly worse prognosis 1

Diagnostic Considerations

• Assessment for autonomic neuropathy should include cardiovascular autonomic reflex tests (CARTs) 1
• Heart rate variability testing is a simple and reliable test of cardiovagal function 2
• A battery of validated autonomic tests rather than a single test is recommended to achieve highest diagnostic accuracy 2
• Screening should include asking about orthostatic dizziness, syncope, or dry cracked skin in extremities 2, 3

Risk Factors and Clinical Correlates

• Age and diabetes duration are major risk factors, with prevalence increasing up to 65% in long-standing diabetes 1
• Glycemic control is a key risk factor, particularly in type 1 diabetes 1
• Presence of other microvascular complications (retinopathy, nephropathy) increases risk 1
• Cardiovascular risk factors including hypertension, dyslipidemia, and obesity increase risk, particularly in type 2 diabetes 1

Treatment Approach

• Gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers are recommended as initial pharmacologic treatments for neuropathic pain in diabetic autonomic neuropathy. 1, 3
• Optimization of glucose control to prevent or delay neuropathy development in type 1 diabetes and slow progression in type 2 diabetes 1, 3
• Management of orthostatic hypotension with increased salt/fluid intake, compressive garments, and medications like fludrocortisone, midodrine, or droxidopa 4, 3
• Treatment of gastroparesis with prokinetic agents and dietary modifications 4
• Management of bladder dysfunction with scheduled voiding and anticholinergic medications when appropriate 1

Clinical Implications

• CAN is a risk marker of mortality and cardiovascular morbidity 1
• Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life 2
• Autonomic neuropathy can occur in isolation or as part of a generalized polyneuropathy 2, 6
• Patients with autonomic neuropathy require careful perioperative management due to increased risk of hemodynamic instability 1