# autonomic neuropathy | Symptoms, Causes, Tests and Treatment | OSANG > Autonomic neuropathy is a group of diseases in which multi-organ dysfunction occurs due to organic damage to autonomic nerve fibers. Diabetes is the most common cause, a… - Official page: https://osns.co.kr/en/encyclopedia/autonomic-neuropathy - Organization: OSANG Neurosurgery ## Page content Neurological Conditions ## autonomic neuropathy Autonomic Neuropathy · G90.0 Autonomic neuropathy is a peripheral neuropathy that causes disorders in involuntary functions such as cardiovascular, digestive, urogenital, sweating, and pupil control due to structural damage to the nerve fibers that make up the autonomic nervous system. ## At a glance Autonomic neuropathy is a group of diseases in which multi-organ dysfunction occurs due to organic damage to autonomic nerve fibers. Diabetes is the most common cause, and autonomic neuropathy is found in approximately 50% of all diabetic patients. The causes are diverse, including autoimmune, hereditary, amyloidosis, post-infectious, and drug-induced, and symptoms appear across the cardiovascular system, digestive system, urinary system, sweating, and pupil function. Diagnosis is made through heart rate variability (HRV) analysis, quantitative sweat axon reflex test (QSART), and skin biopsy, and correction of the cause, symptomatic treatment, and neuromodulation treatment are performed simultaneously. - 01Definition and Overview - 02cause - 03symptoms - 04diagnosis - 05treatment - 06Progress and prognosis - 07life management ## Definition and Overview Autonomic neuropathy is a peripheral neuropathy in which the nerve fibers of the sympathetic nerves and parasympathetic nerves that make up the autonomic nervous system are structurally damaged, resulting in disorders in involuntary body functions such as cardiovascular, digestive, urogenital, sweating, and pupil control. While autonomic dysfunction is a broad concept that includes functional abnormalities, autonomic neuropathy refers to a condition in which organic damage to nerve fibers has been proven. Depending on the cause, autonomic neuropathy is classified into diabetic, autoimmune, hereditary, amyloid, post-infectious, drug-induced, etc. Some form of autonomic neuropathy is observed in approximately 50% of all diabetes patients, and this is a factor that significantly affects the quality of life and prognosis among diabetes complications. Including non-diabetic causes, the prevalence is at a level that cannot be ignored even in the general population, and diagnosis is often delayed due to non-specific symptoms such as chronic fatigue, digestive problems, and dizziness. Autonomic nerve fibers are mostly small fibers with thin (Aδ fibers) or no myelin sheath (C fibers), so it is difficult to detect abnormalities using only existing nerve conduction studies. For this reason, special tests such as heart rate variability (HRV) analysis, quantitative sweat axon reflex test (QSART), and cutaneous nerve biopsy are essential for diagnosis. ## cause ### Diabetic autonomic neuropathy Diabetes is the most common cause of autonomic neuropathy. Chronic hyperglycemia directly damages autonomic nerve fibers through polyol pathway activation, accumulation of advanced glycation end products (AGEs), and oxidative stress. Cardiovascular autonomic neuropathy (CAN) is reported in approximately 50% of patients with type 2 diabetes, and its prevalence increases in proportion to the duration of the disease and the degree of poor glycemic control. Even in type 1 diabetes, autonomic neuropathy develops in approximately 30% of cases 20 years after diagnosis. ### Autoimmune autonomic neuropathy Anti-ganglionic AChR antibody blocks synaptic transmission in autonomic ganglia, causing widespread autonomic dysfunction. Autoimmune autonomic ganglionopathy (AAG) occurs acutely or subacutely and is characterized by severe orthostatic hypotension, gastrointestinal motility disorders, and anhidrosis. In some cases, it responds to immunotherapy, so early diagnosis through antibody testing is important in determining treatment direction. ### Hereditary autonomic neuropathy Hereditary sensory and autonomic neuropathy (HSAN) is a group of diseases in which sensory and autonomic nerve fibers are congenitally defective or degenerative due to genetic mutations. HSAN is classified as types I to V and is characterized by loss of pain sensation, sweating difficulties, repetitive trauma, and ulcers. Autonomic nerve involvement is also prominent in familial amyloid polyneuropathy. ### Amyloid autonomic neuropathy In transthyretin (TTR) amyloidosis, amyloid protein is deposited in autonomic ganglia and nerve fibers, causing nerve damage. Cardiovascular, digestive, and urinary autonomic symptoms appear from the beginning and progress rapidly. AL amyloidosis (light chain amyloidosis) is also accompanied by autonomic neuropathy in approximately 65% of cases. ### Post-infectious autonomic neuropathy Autonomic variants of Guillain-Barr syndrome, HIV-related autonomic neuropathy, and Long COVID-related autonomic dysfunction fall into this category. A mechanism by which the immune response cross-attacks autonomic nerve fibers after infection is proposed. ### Drug-induced autonomic neuropathy Anticancer drugs (cisplatin, vincristine), antiarrhythmic drugs (amiodarone), and some antibiotics (metronidazole) can damage autonomic nerve fibers. The relationship between the timing of drug administration and the onset of symptoms serves as a clue to diagnosis. ## symptoms Symptoms of autonomic neuropathy appear in various ways depending on the distribution area of the damaged nerve, and are characterized by simultaneous manifestations across multiple organ systems. ### cardiovascular symptoms Orthostatic hypotension is the most representative cardiovascular symptom of autonomic neuropathy. Within 3 minutes after standing, systolic blood pressure decreases by more than 20 mmHg, and dizziness, blurred vision, and fainting appear. Resting tachycardia occurs when parasympathetic control is reduced due to damage to the vagus nerve, and a resting heart rate of more than 100 beats/min suggests cardiovascular autonomic neuropathy. Slowed heart rate response during exercise (chronotropic incompetence) and silent myocardial ischemia are also important findings. ### Digestive system symptoms Gastroparesis is a condition that causes early satiety, nausea, vomiting, and abdominal distension due to delayed gastric emptying. Delayed gastric emptying is observed in approximately 20-40% of patients with diabetic autonomic neuropathy. Intestinal motility abnormalities appear as constipation, diarrhea, or an alternation of these, and difficulty swallowing due to esophageal motility disorder also occurs. ### Genitourinary symptoms Bladder autonomic neuropathy causes delayed urination, increased residual urine, nocturia, and overflow incontinence. Bladder dysfunction is reported in approximately 43-87% of diabetic patients. Erectile dysfunction may occur in men, and vaginal dryness and decreased libido may occur in women. ### abnormal sweating Sweating dysfunction is one of the early signs of autonomic neuropathy. Anhidrosis of the distal parts (feet and legs) appears first, followed by compensatory hyperhidrosis of the face and trunk. Reduced sweating leads to impaired body temperature regulation, increasing the risk of heat stroke. Gustatory sweating, that is, abnormal sweating on the face and upper body when eating food, is relatively specific to diabetic autonomic neuropathy. ### pupil abnormality Delayed dark adaptation (slow pupillary dilation response) occurs due to pupil control problems, and patients complain of night vision impairment. Decreased light reflex and delayed pupil constriction response are observed. This is an incidental finding that reflects the degree of progression of autonomic neuropathy. ## diagnosis Diagnosis of autonomic neuropathy is made using a standardized autonomic function test battery. ### Heart rate variability (HRV) analysis Heart rate variability (HRV) is the most widely used noninvasive indicator of autonomic function. In time-domain analysis, RMSSD (root mean square difference of adjacent R-R intervals) reflects parasympathetic activity, and SDNN (standard deviation of R-R intervals) reflects overall autonomic activity. In frequency domain analysis, the high frequency (HF, 0.15~0.4 Hz) component reflects parasympathetic activity, and the low frequency (LF, 0.04~0.15 Hz) component reflects sympathetic-parasympathetic complex activity. A decrease in HRV during a deep breathing test is the most sensitive early indicator of cardiovascular autonomic neuropathy, and heart rate fluctuations of less than 10 beats/min during deep breathing are considered abnormal. ### Valsalva maneuver test After performing forced exhalation (Valsalva maneuver) for 15 seconds at a pressure of 40 mmHg, blood pressure and heart rate response patterns over four stages are analyzed. A Valsalva ratio (maximum heart rate immediately after maneuver / minimum heart rate after maneuver) of less than 1.21 suggests a decrease in parasympathetic function, and loss of stage 4 blood pressure overshoot suggests a decrease in sympathetic function. ### Tilt-table test Continuously monitor the cardiovascular response to passive standing (head-up tilt, 60-70 degree inclination) to differentiate orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), and neurocardiac syncope. A decrease in systolic blood pressure of 20 mmHg or more within 3 minutes of standing is the diagnostic criterion for orthostatic hypotension. ### Quantitative sweat axon reflex test (QSART) QSART (quantitative sudomotor axon reflex test) uses acetylcholine iontophoresis to quantitatively measure the amount of sweating by inducing an axon reflex at the end of the sweating nerve. It is performed on the forearm, proximal lower extremity, distal lower extremity, and foot. Decreased sweating suggests autonomic nerve fiber damage. The sensitivity of the test is reported to be approximately 74% and specificity to be approximately 94%. ### skin biopsy A skin punch biopsy (3 mm) is performed to measure intraepidermal nerve fiber density (IENFD). PGP 9.5-positive small nerve fibers are quantified using immunohistochemical staining, and when they are below the age-sex normal reference value, small nerve fiber loss is diagnosed. It is important as an objective means of confirming autonomic neuropathy because it can simultaneously evaluate the density of the sweating nerves. Gibbons et al. (2009) reported a significant correlation between sweat gland nerve density and QSART results. ### Other auxiliary tests Fasting blood sugar, HbA1c (to screen for diabetes), anti-ganglionic AChR antibody (to check for autoimmune causes), serum protein electrophoresis and immunofixation (to screen for amyloidosis), TTR gene test, and nerve conduction test (to check for damage accompanying large fibers) are used to determine the cause. ## treatment ### Cause Treatment In diabetic autonomic neuropathy, strict blood sugar control is the most important treatment. According to the DCCT (Diabetes Control and Complications Trial) study, the intensive insulin treatment group in type 1 diabetes had a 53% lower risk of developing autonomic neuropathy compared to the conventional treatment group. Autoimmune autonomic neuropathy is treated with immunomodulatory treatments such as intravenous immunoglobulin (IVIG) administration, plasmapheresis, and steroid treatment, and a correlation between a decrease in anti-ganglionic AChR antibody titer and symptom improvement has been reported. The progression of TTR amyloid autonomic neuropathy can be suppressed with transthyretin stabilizers (tafamidis) or gene silencing treatments (patisiran, inotersen). For drug-induced autonomic neuropathy, the priority is to stop or replace the causative drug. ### symptomatic treatment Non-pharmacological approaches are the first line of treatment for orthostatic hypotension. The basics are to increase water intake (2 to 3 L per day), salt supplementation (6 to 10 g per day), elevate the head of the bed (15 to 20 degrees) at bedtime, and wear compression stockings. If drug treatment is necessary, use fludrocortisone (0.1 to 0.3 mg/day) or midodrine (2.5 to 10 mg three times a day). Gastroparesis is managed with small meals (small meals 5-6 times a day), low-fat/low-fiber diet, and gastrointestinal motility stimulants (metoclopramide, domperidone, erythromycin). Regular self-catheterization, alpha-blockers, and cholinergic drugs are used to treat bladder dysfunction. ### neuromodulation treatment Stellate ganglion block (SGB) injects a local anesthetic into the cervical sympathetic ganglion to suppress sympathetic nerve hyperactivation. This can contribute to restoring autonomic balance, improving peripheral blood flow, and normalizing sweating function. Transcranial magnetic stimulation (TMS) is a treatment that helps restore autonomic function by non-invasively stimulating cerebral areas (insula, frontal lobe) related to autonomic nervous system control. Heart rate variability (HRV) biofeedback training is a method in which patients retrain their autonomic reflexes through breathing control, and has been reported to improve cardiovascular autonomic function. ## Progress and prognosis The course of autonomic neuropathy varies greatly depending on the cause. Diabetic cardiovascular autonomic neuropathy progresses in the asymptomatic stage, and the 5-year mortality rate of diabetic patients with confirmed CAN is approximately three times higher than that of patients with normal autonomic function. Asymptomatic myocardial ischemia and fatal arrhythmia are identified as the main mechanisms for increased mortality. Significant recovery is possible in autoimmune autonomic neuropathy if it responds to immunotherapy. However, if the antibody titer is consistently high, it takes a chronic course. Hereditary and amyloid autonomic neuropathies are progressive, but recent advances in gene therapy and amyloid-targeted therapy have made it possible to suppress their progression. Autonomic neuropathy after infection often recovers spontaneously, but in some cases, symptoms persist for several months or years. Drug-induced autonomic neuropathy is expected to gradually recover over several months after discontinuation of the causative drug. Early diagnosis and active management are the keys to improving prognosis. In particular, in diabetic patients, performing autonomic nerve function tests regularly to detect autonomic neuropathy at an asymptomatic stage, strengthening blood sugar control, and starting cardiovascular risk factor management early contributes to reducing mortality. ## life management Daily management of patients with autonomic neuropathy is essential to maintain treatment effectiveness and prevent complications. Water and salt management: Patients with orthostatic hypotension should consume 2 to 3 L of fluid and appropriate salt (6 to 10 g per day) per day. Drinking 500 mL of water before waking up in the morning helps prevent a drop in blood pressure when standing up. Tips for changing posture: When standing up from a lying or sitting position, change your posture slowly, step by step. Sudden standing up, standing still for a long time, or taking a hot water bath can worsen the drop in blood pressure, so caution is required. Meal management: If you have gastroparesis, eat small portions 5-6 times a day and maintain a low-fat, low-fiber diet. If there is a sudden drop in blood pressure after a meal (postprandial hypotension), drinking water before a meal and maintaining a sitting position for 30 minutes after a meal is helpful. Exercise: Regular aerobic exercise (walking, swimming, cycling) is beneficial for improving autonomic function. If orthostatic hypotension is severe, start with lying or sitting exercises (recumbent bike, water exercise). Heat management: If you have sweating problems, you are at increased risk of heat stroke in hot environments, so avoid exposure to direct sunlight and use assistive measures such as cooling vests. Regular checkups: Diabetic patients should monitor their progress by performing autonomic nerve function tests at least once a year. ## Frequently asked questions ### Q01What symptoms do I experience if I have autonomic neuropathy? Symptoms of autonomic neuropathy vary depending on the distribution area of the damaged nerve. Typical symptoms include dizziness or fainting when standing up, bloating or constipation after eating, difficulty urinating or feeling of residual urine, abnormally excessive or low sweating, dry eyes, and a feeling of fast or irregular heartbeat. It is characteristic that symptoms appear simultaneously in multiple organs, so if you have complex symptoms whose cause is unknown, we recommend that you undergo an autonomic nerve function test. ### Q02Is it necessary to develop autonomic neuropathy if you have diabetes? Not all diabetic patients develop autonomic neuropathy. However, autonomic neuropathy is observed in approximately 50% of all diabetic patients, and the risk of developing it increases as blood sugar control is poor or the duration of the disease is long. Strict management of blood sugar levels early can slow the onset and progression of diabetes, so it is recommended to undergo regular autonomic nerve function tests from the beginning of diabetes diagnosis. ### Q03How is autonomic neuropathy diagnosed? An autonomic function test battery, including heart rate variability (HRV) analysis, standing tilt table test, and Valsalva maneuver test, is performed. If a sweating abnormality is suspected, quantitative sweat axon reflex testing (QSART) may be added and a skin biopsy may be performed to check for fibrillar damage. At Osang Neurosurgery, we comprehensively perform these tests to precisely evaluate the extent and severity of autonomic nerve damage. ### Q04Is autonomic neuropathy treatable? Treatment policy and prognosis vary depending on the cause. The key to diabetic autonomic neuropathy is thorough blood sugar management, and autoimmune autonomic neuropathy may show significant improvement with immunoglobulin (IVIG) administration or plasmapheresis. Symptomatic treatment can control orthostatic hypotension, digestive disorders, and urinary symptoms, and neuromodulation treatments such as stellate ganglion block or transcranial magnetic stimulation (TMS) can help restore autonomic balance. Don't give up, consult with a specialist and create a treatment plan that's right for you. ### Q05Are autonomic neuropathy and dysautonomia different? Autonomic neuropathy refers to a condition in which organic (structural) damage to autonomic nerve fibers has been confirmed, and dysautonomia is a broader concept that includes functional abnormalities. Autonomic neuropathy differs in that nerve damage can be objectively confirmed through skin biopsy or quantitative testing. We recommend that you undergo an autonomic nerve function test to make an accurate distinction. ### Q06Is there anything patients with autonomic neuropathy should be careful about in their daily lives? If you have orthostatic hypotension, stand up slowly and gradually, maintain daily water intake of 2 to 3 liters or more, and consume appropriate salt. Caution is needed in high-temperature environments or standing for long periods of time as this can worsen the decline in blood pressure. If you have digestive problems, eat small portions (multiple meals) and regular light exercise helps restore balance to your autonomic nervous system. Please consult a specialist for specific life management plans. ### Q07Is it dangerous if autonomic neuropathy progresses? As cardiovascular autonomic neuropathy progresses, the risk of subclinical myocardial ischemia, arrhythmias, and sudden cardiac death may increase. It has been reported that the 5-year mortality rate for patients with diabetic cardiovascular autonomic neuropathy is approximately three times higher than for patients with normal autonomic function. Therefore, it is important to detect it early and actively manage it. If you suspect any symptoms, do not delay and get an autonomic nervous system examination. ## Related articles - delirium - Cervical radiculopathy - Cervical disc herniation - dystonia This article provides general medical information and does not replace an individual diagnosis or treatment plan. 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