para>Cardiac autonomic neuropathy can cause loss of sensation associated with myocardial ischemia (1). ‚
DIFFERENTIAL DIAGNOSIS
- Overall
- Multiple sclerosis is central nervous system disorder with similar symptoms.
- Cardiac
- Neurocardiogenic syncope
- Cardiogenic syncope: long QT syndrome, hypertrophic obstructive cardiomyopathy, Brugada syndrome, and so forth
- Sick sinus syndrome
- Pheochromocytoma
- Gastrointestinal
- Celiac disease
- Inflammatory bowel disease
- Erectile symptoms
- Cardiovascular
- Psychogenic
- Urinary
- Stress or urge urinary incontinence
- Lower urinary tract symptoms from prostate hypertrophy
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Elevated resting heart rate is the most important single sign of cardiac autonomic neuropathy. A resting HR of >90 has a 43% positive predictive value (PPV) for cardiac autonomic neuropathy (CAN) (6)[B].
- Orthostatic tolerance testing: characterized by systolic blood pressure drop of >20 mm Hg or diastolic drop of >10 mm Hg 3 minutes after standing with minimal heart rate response (7)[B]
- Electrocardiogram for resting abnormalities predisposing to syncope (7)[C]
- Fasting blood glucose and A1c testing
- HIV testing " ”HIV infection associated with autonomic neuropathy (3)[C]
- Erythrocyte sedimentation rate and/or C-reactive protein to screen for collagen vascular disease
Follow-Up Tests & Special Considerations
- Echocardiogram and ambulatory electrocardiogram
- Collagen vascular disease workup if other suggestions of autoimmune condition (likely to be mixed connective tissue): antinuclear antibody, anti-Scl-70, ACA, anti-RNA, SS-A, SS-B (3)[C]
Diagnostic Procedures/Other
- Nerve conduction studies to quantify effects on sensory and motor peripheral nerves (3)[C]
- Autonomic function testing: test parasympathetic, sympathetic, and cholinergic system function with timed responses to stimuli. Heart rate variability testing by ambulatory monitoring or clinic-based testing (7)[C].
- Gastric emptying studies for postprandial satiety, nausea, and vomiting. Unless known poorly, controlled diabetes should be preceded by endoscopy and imaging (8)[C].
- Urodynamic studies can confirm neurogenic bladder (9)[C].
Test Interpretation
A negative orthostatic test at 3 minutes may miss a portion of patients with delayed orthostatic hypotension (7)[B]. ‚
TREATMENT
GENERAL MEASURES
- Control of diabetes is most important for control of diabetic autonomic neuropathy. The evidence of intensive glucose control is strong for type 1 diabetes, but less so for type 2 (3)[C].
- Exercise shown to improve cardiac autonomic neuropathy in diabetic patients, although patient-oriented outcomes were not measured (5)[B].
- Volume repletion up to 10 L per day and salt repletion up to 10 g daily is first-line treatment for orthostatic hypotension (3)[C].
- Eating small meals and lowering the fat content of the diet can help with gastroparesis (3)[C].
MEDICATION
First Line
- Orthostatic hypotension: if volume repletion is not successful, start 9-α-fluorohydrocortisone at 0.1 to 0.3 mg daily (3)[C]
- Gastroparesis: can improve gastric emptying with a prokinetic agent such as metoclopramide. Erythromycin tends to lose effect over time (8)[C].
- Constipation: osmotic laxatives. Possible lubiprostone (8)[C]
- Diarrhea and constipation can be due to small bowel overgrowth predisposed by autonomic neuropathy.
- Avoid proton pump inhibitors (10)[C].
- Consider trial of rifaximin for 7 to 10 days (10)[B].
- Consider probiotics (10)[B].
- Erectile dysfunction: A phosphodiesterase 5 inhibitor can overcome most neuropathic effects (3)[C].
- Urinary tract dysfunction: Cholinergic medications can show modest symptom effects (3)[C].
Second Line
- Orthostatic hypotension: can add midodrine to 9-α-fluorohydrocortisone but must be careful of dose and sensitivity to medication (3)[C].
- Erectile dysfunction: corpus cavernosum injection therapies and prosthetics if necessary (3)[C]
- Urinary overflow incontinence often requires intermittent self-catheterization (9)[C].
ISSUES FOR REFERRAL
Refer any patient without diabetes or known cause for autonomic neuropathy to neurology for workup ‚
SURGERY/OTHER PROCEDURES
- If gastroparesis is poorly controlled, gastric pacing or performance of a partial gastrectomy may be necessary (8)[C].
- May require surgical bladder replacement for neurogenic bladder (9)[C]
COMPLEMENTARY & ALTERNATIVE MEDICINE
Acupuncture has been proposed for autonomic neuropathy treatment. Evidence of benefit is limited to small studies of poor quality and potential for bias despite uniformly positive results (11,12)[A]. ‚
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
For diabetic patients, autonomic neuropathy is a marker for increased cardiovascular and overall mortality, so patients should follow up more frequently (2)[C]. ‚
PROGNOSIS
The presence of autonomic neuropathy increases 8-year mortality from 8% to 27% overall for diabetics (2). ‚
COMPLICATIONS
Autonomic neuropathy can reduce symptoms of hypoglycemia, making intensive insulin control more dangerous (2). ‚
REFERENCES
11 Dimitropoulos ‚ G, Tahrani ‚ AA, Stevens ‚ MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes. 2014;5(1):17 " “39.22 Vinik ‚ AI, Maser ‚ RE, Mitchell ‚ BD, et al. Diabetic autonomic neuropathy. Diabetes Care. 2003;26(5):1553 " “1579.33 Freeman ‚ R. Autonomic peripheral neuropathy. Lancet. 2005;365(9466):1259 " “1270.44 Verhoeven ‚ K, Timmerman ‚ V, Mauko ‚ B, et al. Recent advances in hereditary sensory and autonomic neuropathies. Curr Opin Neurol. 2006;19(5):474 " “480.55 Voulgari ‚ C, Pagoni ‚ S, Vinik ‚ A, et al. Exercise improves cardiac autonomic function in obesity and diabetes. Metabolism. 2013;62(5):609 " “621.66 Ge ‚ X, Pan ‚ SM, Zeng ‚ F, et al. A simple Chinese risk score model for screening cardiovascular autonomic neuropathy. PLoS One. 2014;9(3):e89623.77 Weimer ‚ LH. Autonomic testing: common techniques and clinical applications. Neurologist. 2010;16(4):215 " “222.88 Gatopoulou ‚ A, Papanas ‚ N, Maltezos ‚ E. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice. Eur J Intern Med. 2012;23(6):499 " “505.99 McDougall ‚ AJ, McLeod ‚ JG. Autonomic neuropathy, I. Clinical features, investigation, pathophysiology, and treatment. J Neurol Sci. 1996;137(2):79 " “88.1010 Bures ‚ J, Cyrany ‚ J, Kohoutova ‚ D, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010;16(24):2978 " “2990.1111 Chen ‚ W, Yang ‚ GY, Liu ‚ B, et al. Manual acupuncture for treatment of diabetic peripheral neuropathy: a systematic review of randomized controlled trials. PLoS One. 2013;8(9):e73764.1212 Franconi ‚ G, Manni ‚ L, Schr ƒ ¶der ‚ S, et al. A systematic review of experimental and clinical acupuncture in chemotherapy-induced peripheral neuropathy. Evid Based Complement Alternat Med. 2013;2013:516916.
ADDITIONAL READING
Balcio „ Ÿlu ‚ AS, M ƒ ¼derriso „ Ÿlu ‚ H. Diabetes and cardiac autonomic neuropathy: clinical manifestations, cardiovascular consequences, diagnosis and treatment. World J Diabetes. 2015;6(1):80 " “91. ‚
CODES
ICD10
- G90.9 Disorder of the autonomic nervous system, unspecified
- E11.43 Type 2 diabetes w diabetic autonomic (poly)neuropathy
- E10.43 Type 1 diabetes w diabetic autonomic (poly)neuropathy
- E13.43 Oth diabetes mellitus w diabetic autonomic (poly)neuropathy
- G90.09 Other idiopathic peripheral autonomic neuropathy
- E08.43 Diab due to undrl cond w diabetic autonm (poly)neuropathy
ICD9
- 337.9 Unspecified disorder of autonomic nervous system
- 337.1 Peripheral autonomic neuropathy in disorders classified elsewhere
- 250.60 Diabetes with neurological manifestations, type II or unspecified type, not stated as uncontrolled
- 250.61 Diabetes with neurological manifestations, type I [juvenile type], not stated as uncontrolled
- 337.00 Idiopathic peripheral autonomic neuropathy, unspecified
- 337.09 Other idiopathic peripheral autonomic neuropathy
SNOMED
- Autonomic neuropathy (disorder)
- Diabetic autonomic neuropathy (disorder)
- Diabetic autonomic neuropathy associated with type 2 diabetes mellitus
- Diabetic autonomic neuropathy associated with type 1 diabetes mellitus
- Autonomic neuropathy due to amyloid (disorder)
- Disorder of peripheral autonomic nervous system (disorder)
CLINICAL PEARLS
- Autonomic effects are often subclinical in peripheral neuropathies.
- Autonomic neuropathy is a marker for poorly controlled diabetes and significant increases mortality risk.
- A resting heart rate of >90 bpm, especially if persistent, should increase concern for autonomic neuropathy.
- Exercise can improve autonomic function in diabetics and prediabetics.
- Erectile dysfunction in diabetes may be an initial marker for autonomic neuropathy.