Since 1996 [1], the neurology leadership, the American Academy of Neurology (AAN), has published seminal articles regarding clinical purpose and applicability of P&S monitoring. The general consensus from these articles is that inflammatory and demyelinating diseases, pain, dizziness, and sleep disorders are associated with, or result from, AN. The 1996 article [1] reports on the “uses of tests of autonomic function. Consensus on the usefulness of tests of autonomic function exists for a number of disorders and conditions. These tests, in general, are definable in terms of their ability to diagnose a condition, to provide unique differential diagnostic information, or to quantify those aspects of autonomic function that have an impact on outcome or evaluate treatment efficacy.” In the article, the Therapeutics and Technology Assessment Subcommittee states [1, p. 876], “patients need to be studied for several reasons. Diagnosis might not be possible without autonomic studies.” The AAN states “There are several special clinical reasons for utilizing tests of autonomic function. There is increasing evidence that the function of [autonomic] nerve fibers may improve as neuropathy improves… Autonomic cardiovascular indices correlate with [autonomic] function… As the cardiovascular autonomic neuropathy [CAN] worsens, the cardiovascular performance and systemic peripheral resistance responses become more abnormal. Another reason for autonomic evaluation is that patients with autonomic failure show an increase in mortality.” Since 1996, increased mortality has been recognized as a result of CAN, and CAN is treatable [1, p. 873, 2].

Noninvasive autonomic tests have an extremely high value to risk ratio [1, p. 875]. The article lists conditions whose diagnoses benefit from P&S monitoring [1, p. 876]. “The twin attributes of quantization and non-invasiveness render autonomic evaluation ideally suited to monitor the alterations of autonomic function over time. A numeric score is available.” “These studies can differentiate among several related types of disorders; for instance, separating Parkinson’s disease from multiple system atrophy (MSA) and Shy-Drager syndrome, disorders whose autonomic burden differs in severity and distribution and is predictive of subsequent outcome” [1, p. 876]. On the basis of a movement disorder (early Parkinson’s), P&S monitoring helps to detect AD before (1) secondary disorders exacerbate the primary and (2) differentiate, early, MSA from Parkinson’s disease to improve outcomes. Note, MSA preserves cardiac sympathetic innervation, and Parkinson’s disease does not [3–5].

The subcommittee continues and lists diabetes, amyloidosis, Sjögren’s syndrome, immune-mediated neuropathies, panautonomic neuropathy, idiopathic autonomic neuropathy, paraneoplastic neuropathy, peripheral autonomic neuropathies, pure autonomic failure (PAF), syncope, orthostasis (including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension), chronic pain (including differentiating sympathetically mediated pain and reflex sympathetic dystrophy (RSD), now chronic regional pain syndrome (CRPS), and causalgia), Lambert–Eaton myasthenic syndrome, Chagas’ neuropathy, leprosy, and abnormal sweating. Also included in the list is patients’ beta-blocker response. They state that P&S monitoring involves “differentiation of benign from life-threatening autonomic disorders. Certain autonomic disorders mimic the more malignant generalized autonomic disorders.” The subcommittee recommends autonomic monitoring “to clarify the differential diagnosis… autonomic tests revealing autonomic balance [sympathovagal balance, or SB], … demonstrate asymmetry of vasomotor and sudomotor activity as indices of such over-action and to establish the pattern of such dysfunction” [1, p. 876].

The AAN recommends P&S monitoring for “evaluation of the response to therapy. The autonomic deficits may lessen in response to treatment. When therapy is applied, quantitative methods are needed to evaluate if the response to therapy is adequate” [1, p. 876]. P&S monitoring quantitates and documents patient response to therapy, disease, lifestyle, and history. In addition, they recommend the combination of tilt study and autonomic screening, to demonstrate indices of orthostatic intolerance, or those of autonomic failure, which aid in treatment and follow-up [1, p. 876]. P&S monitoring with the Autonomic Assessment’s 5 min resting and 5 min PC challenges satisfies this recommendation [6].

In 1999, the American Heart Association (AHA) issues a scientific statement [7], which was supported by a joint editorial from the American Diabetes Association (ADA); the Juvenile Diabetes Research Foundation (JDRF); the National Institutes of Health (NIH); the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDKD); and the AHA [8]. The AHA states “that autonomic nervous system testing is an effective and accepted method for early detection of sub-clinical cardiovascular diseases (CVDs), … the leading cause of death in the United States since 1990… One American will die every 33 s of CVD every day” [7, p. 1143]. The AHA “also recommends interventions to reduce risk for patients with established CVD” [7, p. 1143]. “Autonomic testing to determine autonomic dysfunction is a standard of care for detecting both clinical and sub-clinical CVD, and is recognized and recommended by the [AHA]” [7, p. 1138].

“Earlier detection of CVD extends overall survival, improves quality of life, decreases the need for intervention procedures such as angioplasty, coronary artery bypass graft surgery, and reduces the risk of subsequent myocardial infarctions, and ischemic events” [7, p. 1143]. Autonomic dysfunction predisposes a patient to life threatening CVD, … and carries a 50 % mortality rate in five years [9, 10]…. Patients do respond to secondary CVD prevention and interventions [7, p. 1139].

CVD may be detected very early (in the subclinical phase) through P&S monitoring. In fact, P&S assessment includes components of stress testing, EKG monitoring, tilt table studies, sitting–standing BP testing, event monitoring, Holter monitoring, cardiac output testing, ambulatory BP testing, and vascular studies. With diabetes as a model of chronic disease, the AHA references hypertension, cardiomyopathy, congestive heart failure, cardiac ischemia (including angina), dyspnea on exertion, cerebrovascular disease, coronary artery disease, coronary heart disease, cardiac dysrhythmias, left ventricle dysfunction, peripheral artery disease (including atherosclerosis), mitral valve dysfunction, and myocardial infarction as types of CVDs [7]. P&S monitoring quantifies and documents autonomic involvement in CVD and patient responses to CVD therapy, which involves autonomically active medications (e.g., beta-blockers and antihypertensives, see Table 6.​2).

Beginning in 2003 [9], the ADA has published a series of articles on the standard of care for diabetic neuropathies [11–13]. The ADA states that “The economic impact of the recommendation to use autonomic function testing is minimal compared with the economic impact of the catastrophic events related to advanced cardiovascular, cerebrovascular, and renal complications. The relative cost of testing will always be less than the incremental costs of treating either a detected complication or the more catastrophic event that could eventually occur” [9, p. 1573]. In this standards of care article entitled “Diabetic Autonomic Neuropathy,” the ADA recommends P&S testing as part of the standard of care for diabetes.

The ADA describes diabetic autonomic neuropathy (DAN) as “a serious and common complication of diabetes…. Major clinical manifestations of DAN include resting tachycardia (>100 bpm), exercise intolerance, orthostatic hypotension (a fall in systolic blood pressure >20 mmHg upon standing), constipation (possibly alternating with episodes of diarrhea), gastroparesis, erectile dysfunction or retrograde ejaculation, bladder dysfunction, sudomotor dysfunction, impaired neurovascular function, ‘brittle diabetes’, and hypoglycemic autonomic failure, as well as other disturbances in P and S function involving the skin, pupils, esophagus” [9, p. 1553,12, 13]. As you know, DAN is a precursor to CAN which carries a 50 % increase in the 5-year mortality rate [7]. “CAN is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function … is strongly associated with an increased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of autonomic function tests” [9, p. 1553] (see Chap. 5). “[CAN] is the most prominent focus because of the life-threatening consequences of this complication … and the availability of direct tests of cardiovascular autonomic function…. CAN results from damage to the autonomic nerve fibers that innervate the heart and blood vessels and results in abnormalities in HR control and vascular dynamics. Reduced [autonomic function] is the earliest indicator of CAN” [9, p. 1556].

“The consensus statement sponsored by the ADA and AAN was a synthesis of reviewed research efforts to date in the clinical assessment of neuropathies and offered recommendations for the testing of diabetic neuropathy (including autonomic neuropathy)…. Specifically concerning the assessment of CAN, the panel recognized strong evidence for the three tests of HR control. The three tests recommended were HR response to: (1) deep breathing, (2) standing, and (3) the Valsalva maneuver…. These tests were judged suitable for both routine screening and monitoring the progress of autonomic neuropathy [9, p. 1570].

Boulton et al. [11] refined the 2003 ADA statement and observe that autonomic neuropathy “may involve every system in the body, causes substantial morbidity, and increased mortality particularly if [CAN] is present…. Effective treatments are available for … autonomic neuropathy” [11, p. 956]. “At time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of autonomic dysfunction earlier), patients should be screened for CAN” [11, p. 958]. “Sudden death and silent myocardial ischemia have been attributed to CAN” [11, p. 957]. “Regular [autonomic] testing provides early detection and therapy and thereby promotes timely diagnostic and therapeutic interventions…. testing may also facilitate differential diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, dizziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction encourages patient and physician to improve metabolic control and to use therapies, such as ACE inhibitors and beta-blockers, which are proven to be effective for patients with CAN…. Cardiac autonomic function testing should be performed when planning an exercise program for individuals …, especially those at high risk for underlying [CVD]” [11, p. 958]. Again, P&S monitoring quantifies and documents autonomic involvement in disease and quantifies and documents patient responses to therapy, therapy which involves autonomically active medications (e.g., beta-blockers and antihypertensives).

By inclusion, the ADA extend the 2003 [9] and 2005 [11] standards of care statements [12, 13]. “Autonomic neuropathy can increase the risk of exercise-induced injury or adverse event through decreased cardiac responsiveness to exercise, postural hypotension, impaired thermoregulation, impaired night vision due to impaired papillary reaction, and unpredictable carbohydrate delivery from gastroparesis predisposing to hypoglycemia…. People with diabetic autonomic neuropathy should undergo cardiac investigation before beginning physical activity more intense than that to which they are accustomed” [12, p. S23, 13]. “Teaching people with diabetes to balance insulin use, carbohydrate intake, and exercise is a necessary but not always sufficient strategy. In type 1 diabetes and severely insulin-deficient type 2 diabetes, the syndrome of hypoglycemia unawareness, or hypoglycemia-associated autonomic failure, can severely compromise stringent diabetes control and quality of life. The deficient counter-regulatory hormone release and autonomic responses in this syndrome are both risk factors for, and caused by, hypoglycemia” [12, p. S24, 13].