The following sections attempt to answer the questions, “Why test?”, “How to intervene?”, and “What are the expected outcomes?”

The ANS controls or coordinates all cells and all systems of the human body. Typically, patients do not present with symptoms until end-organ dysfunction is demonstrated. The function of the PSNS and SNS is to work together to maintain homeostasis and prevent end-organ dysfunction, even when they are functioning in degraded modes such as in the face of disease processes. P&S dysfunction is more, and perhaps earlier, information that is treatable and may help to reduce or relieve morbidity or mortality risk. As recognized by the American Diabetes Association and the American Association of Clinical Endocrinologists, autonomic dysfunction may be present (asymptomatically) long before the disease is diagnosed. This is the logic behind recommending autonomic testing at or soon after the time of diagnosis. In type 2 diabetes, it is expected that the diseases has been present for up to 5 years prior to diagnosis. Evidence suggests that upon first autonomic assessment, up to half of the available P&S function is lost as compared with age-matched normals [1]. Similar evidence has been documented for other chronic diseases [2–4].

Early detection of autonomic dysfunction may lead to early intervention, even before symptoms. Early intervention may be low dose and short term, just enough to retrain the PSNS or SNS to establish and maintain normal SB and allow the ANS to carry forward independently. This reduces morbidity and mortality risk (even in patients after symptoms are demonstrated, but before end-organ damage), reduces medication load and hospitalizations, improves patient outcomes, and reduces healthcare costs, both for the patient and the healthcare system as a whole.

SB is a measure of the relative, resting levels of P&S activity. Many medications are directly or indirectly autonomically active. The obvious medications are beta-blockers, antihypertensives, antidepressants, bronchodilators, and vasopressors. Less obvious medications include statins [5], as an example. Proper autonomic responses to medications lead to a normalization of SB. Titrating therapy to establish and maintain the proper SB guides therapy specifically for the individual patient, based on her/his own physiology and history. This has been shown to reduce morbidity and mortality risk, ameliorate symptoms, reduce medication load and hospitalization, improve patient outcomes, and reduce healthcare costs [6, 7].

P&S monitoring is an objective, reliable, reproducible, comprehensive, and robust means of providing autonomic assessment in a physician’s office. The large academic centers for autonomic testing typically see the “10 % worst cases” of autonomic dysfunction. However, it is well known that many conditions involve autonomic dysfunction. P&S monitoring, due to overt autonomic symptoms or the diagnosis of chronic disease, documents patient’s P&S responses at rest and in response to challenge. P&S monitoring provides information similar to Holter monitoring results. The DB challenge simulates conditions that exist after large meals or before retiring for the night. The Valsalva challenge simulates conditions, such as during exercise or psychological or physiological stress. The initial baseline simulates resting conditions and the stand challenge simulates postural changes, e.g., from supine to sitting and from sitting to standing. In fact, the stand challenge elicits postural change responses much the same as a tilt-table studies [8]. All P&S monitoring objectively documents patient responses to disease, therapy, lifestyle, genetics, injury, and surgery. P&S monitoring is clinically trendable, fulfilling the requirements for documenting clinical outcomes.

P&S monitoring facilitates detecting, differentiating, and documenting the P and S dysfunction that precedes, underlies, exacerbates, and sometimes causes symptoms, diseases, and disorders, including cardiovascular, endocrine, GI, neurological (including sleep and pain management), osteopaths, pulmonary, and urogenital diseases [6, 9–16]. Independent, simultaneous P&S monitoring adds more information to what physicians currently measure and know, including, as discussed herein, hidden parasympathetic excess (PE), Valsalva sympathetic excess (SE), and sympathetic withdrawal (SW) upon standing [17, 18]. Therefore, P&S monitoring provides more evidence to improve the differential diagnosis, thereby, improving patient care. P&S monitoring detects, differentiates, and documents autonomic dysfunction prior to autonomic neuropathy, including CAN, and prior to the onset of comorbidities. Autonomic comorbidities include CAN with PE or CAN with SE. For example, CAN with PE is associated with (subclinical) depression, including depression associated with cardiovascular disease, anxiety, bipolar, attention disorders, etc. [17]. CAN with SE is associated with hypertension, COPD, or sleep apnea [19, 20]. CAN with SE is also possible from a single (asymptomatic) hypoglycemic event in patients with diabetes [21–23]. P&S monitoring provides more information, including when ordered with common tests (see Appendix 3), helping to guide selection and titration of therapy, and further testing leading to improved patient outcomes and reduced healthcare costs.

Follow-up testing is required to document patient response to disease and therapy. P&S monitoring documents compliance with therapy (e.g., CPAP [20]) and, for example, ensures CAN risk is minimized and remains minimized [24]. It also documents rehabilitation [14]. CAN increases risk of mortality and morbidity [25, 26], for example, when tighter glycemic control is attempted [21]. CAN often precedes other cardiac risk indicators, such as low ejection fraction [27, 28]. P&S monitoring detects early SE that leads to heart disorders prior to cardiomyopathy or the often asymptomatic effects of heart disorders prior to heart failure, MI, or ischemia [12]. Early detection leads to early intervention when short-term or proactive intervention is possible. In geriatrics and cardiovascular disease patients, including post-MI or post-CABG patients, depression can increase risk of mortality [29–34]. P&S monitoring detects the PE associated with depression. PE cannot be objectively measured with any other device [17]. As another example, in geriatrics, P&S monitoring documents risk of falling and may be applied to prevent falls.

A well-documented example of the potential for autonomic testing is the ACCORD study. In part, the failure of the ACCORD study was due to the fact that a single hypoglycemic event may induce (asymptomatic) CAN. Asymptomatic CAN causes the secondary symptoms associated with chronic disease, including diabetes. Subsequent tight glycemic control may simulate a second glycemic event. Glycemic events induce SE, which, in the presence of CAN, causes sudden cardiac death. Independent, simultaneous P&S monitoring detects both CAN and SE [21–23].

Another common example is from sleep apnea [20]. There may be a need for additional sympathetic blockade to normalize SE if CPAP is not sufficient. Remember, CPAP is not a sympatholytic. CPAP, in effect, reduces the “stress” of not breathing at night and therefore not sleeping well. If SEs existed prior to sleep apnea, especially if sleep apnea is a secondary disorder, then it is likely that those SEs will persist after CPAP. This means the mortality risks of SEs persist after CPAP. Often this is not known until very late in the progression of cardiovascular disease secondary to sleep apnea. Detection of extant SE, even when asymptomatic, prevents secondary cardiovascular diseases that often lead to increased medication load, hospitalizations, and morbidity and mortality.

P&S monitoring provides more information and more evidence to help document and differentiate diagnoses and to help guide therapy for the individual patient, improving outcomes.

Low-cost, independent, simultaneous P&S monitoring identifies, differentiates, and documents patients’ responses to disease and therapy, enabling therapy modifications prior to the development of comorbidities [6, 9, 11–13, 16]. P&S monitoring documents patient compliance with therapy and treatments [14], thereby documenting individual patients in whom outcomes are not improved. Differentiating specific P and S dysfunctions guides therapy selection, minimizing trial and error. Early detection of P&S imbalance enables preventative interventions that reduce hospitalizations, the potential for lifelong therapy, and healthcare costs [6].

For example, in hypertensives, diabetics, and other chronic disease patients, detecting CAN early enables intervention that reduces medication load and hospitalizations due to complications of heart disease [6]. P&S monitoring in pain management also reduces workman’s compensation costs [14]. In hypertensives, it reduces (1) the amount of, and need for, long-term therapy, (2) associated comorbidities, and (3) hospitalizations due to stroke, aneurysms, kidney disease, and heart disease [6, 13, 35, 36]. These reductions improve patient outcomes and reduce healthcare costs. Medications, supplements, and therapies on the market are implicated in increasing morbidity and mortality risk in subpopulations of patients [37, 38]. Low-cost, independent, simultaneous P&S monitoring documents patient responses to these agents as well, minimizing poorer outcomes.

In cases where patients have a history of anticholinergic therapies (e.g., depression, anxiety, bipolar, ADD/ADHD, fibromyalgia, etc.) for more than 3 months and with P&S monitoring, the patients demonstrate PE; then it is reasonable to consider the efficacy of the therapy. It may be that the therapy is merely masking symptoms and not addressing an underlying cause (PE). This seems to be especially true when it is obvious when the patient has skipped doses of the anticholinergic therapy. In other words the patient is not responding as expected to their current medication. Often switching therapy to a different agent will also address the PE. Typically, these patients require lower dose and then, as the PE is relieved, are required to self-wean, without it being obvious that they skipped dosing. If upon follow-up P&S testing, the PE is relieved and the patient is stable, the anticholinergic therapy may be discontinued and the patient may carry forward unmedicated until some other clinical event occurs. Overall this helps to reduce healthcare costs.

As a last example, we will address pain management. P&S monitoring (1) objectively quantifies pain level; (2) provides more information to differentiate non-physiologic pain, from physiologic pain, from CRPS; (3) provides more information to guide titration of (often highly addicting) medication; and (4) documents rehabilitation. In all four instances, more value is added. Objective quantification of pain level aids in tailoring each physical therapy session, regardless of patient’s psychological state. Differentiating non-physiologic pain from physiologic pain reduces the chances of excess dosing. Differentiating CRPS, especially earlier, may lead to (earlier) additional therapies that may help to avoid lifelong medication. Tailoring titration of therapy may reduce therapy levels and prevent the additional costs of treating addictions. Documenting rehabilitation may help to return patients to a productive lifestyle and eliminate dependencies on the state.

Overall, P&S monitoring helps to add value to clinical practice and ultimately reduces healthcare costs while improving patient outcomes.

The additional information from independent, simultaneous P&S monitoring reveals underlying patient physiology that guides therapy decisions and reduces trial and error in prescribing for primary as well as secondary diseases and disorders [10, 14, 24, 39]. The additional information from P&S monitoring guides and documents referral decisions and the need for additional testing. P&S monitoring documents patient compliance and detects abnormal conditions early, enabling more relaxed and perhaps preventative interventions, thereby reducing high cost emergency, rescue interventions, and improving patient outcomes [6, 39, 40]. This additional information reduces morbidity and mortality risk associated with P and S dysfunction [25, 26]. Common tests cannot detect or document isolated P or S dysfunction [41], and P and S dysfunction cannot be treated unless measured.

For example, in sleep apnics [20], P&S monitoring is a physiologic measure of CPAP compliance and documents whether CPAP is sufficient or additional sympathetic blockade is required to prevent hypertension, heart disease, and sudden death from CAN and other complications due to sleep apnea. Another example is therapy decisions for depression, including documenting when patients are not responding to specific anticholinergic agents. If the patient’s PE persists, then a different anticholinergic (antidepressants, e.g., tricyclics, SNRIs, or SSRIs) may be required [17]. Only P&S monitoring is able to document the PE. For patients who report dizziness, only P&S monitoring is able to document SW, PE, or SE, as they are associated with postural change abnormalities. Correcting these abnormalities relieves dizziness associated with syncope, orthostasis, and possibly arrhythmia and reduces the risk of falling [17].

P&S monitoring augments many common test modalities (see Appendix 3). Except for neurological tests (including sleep studies), these test modalities test smooth or cardiac muscle function. As it is well known, all muscles, including smooth and cardiac muscle, are innervated. Smooth and cardiac muscles are innervated by P and S nerves. P&S monitoring together with these tests helps to differentiate muscle from nerve dysfunction. For example, pulmonary function testing determines lung capacity. Lung capacity is a function of both bronchial diameter and ventilatory efficacy. The SNS directly controls bronchial diameter and the PSNS directly controls ventilation. Just because lung capacity is low does not mean the cause has been differentiated. It may still not be obvious as to whether there is a sympathetic or parasympathetic dysfunction involved. This of course guides therapy, for assuming a sympathetic dysfunction and prescribing adrenergic agents may exacerbate an actual parasympathetic dysfunction and vise versa.

As another example, if in a patient with a lower body vascular disorder (e.g., orthostatic hypotension, varicose veins, etc.), the vascular study leads to a diagnosis of vascular insufficiency due to “lazy walls” (and the valves are found to be functioning), the thought may be that the smooth muscle controlling the veins is dysfunctional. While this is correct, is it known a priori whether is it truly the smooth muscles that are dysfunctional or is it the sympathetic innervation that is dysfunctional. P&S monitoring will determine the presence of autonomic dysfunction (e.g., SW). Treating SW may be lower-cost and shorter-term therapy than treating the smooth muscle dysfunction.

Nerve studies tend to measure sensory and motor nerves, the larger “A” and “B” nerve fibers. P&S monitoring measures the autonomic nerve responses which represent some of the small “C” nerve fibers. If it can be felt, paralysis or paresthesia, it is not autonomic.

Similar stories are available for many other tests (e.g., cardiac studies test the mechanical and electrical properties of the heart muscle itself; autonomic innervation of the heart is at best only inferred; GERD may be due to either PE or, indirectly, SE; tilt-table studies are often unrevealing; etc.). P&S testing provides a comparison test to help differentiate the diagnosis and perhaps further specify the dysfunction and therefore more accurately guide therapy.

Since the inception of the Physician Quality Reporting Initiative (PQRI) program, the measures listed cover many of the ICD-9 codes typically reimbursed for P&S monitoring (see Appendix 2). Consistently, nearly 70 % of the PQRI measures are objectively documented by the Multi-Parameter Graph Report available from P&S monitoring.

The two diseases that affect the most people in the United States are hypertension and diabetes (2010). Hypertension is diagnosed in over 60 million patients [42], and diabetes is diagnosed in over 40 million patients [43]. Heart disease, Parkinson’s disease, and COPD are significant within the geriatric patient population, and sleep apnea, pain, and depression are significant in the younger patient populations. Like most chronic diseases, all of these chronic diseases or disorders over time (even when maintained) are known to also generate comorbidities that increase medication load and hospitalizations, increasing healthcare costs for the individual patient, as well as for the nation. A major cause of comorbidities in chronic diseases is P&S dysfunction (imbalance) that ultimately leads to autonomic neuropathy and increased morbidity and mortality risk. This is why the leadership¹ has recommended P&S monitoring as part of the standard of care [44–48].

The strength of P&S monitoring comes from the nature of the P and S nervous systems themselves. The P and S nervous systems control and coordinate all other systems within the body [42, 43, 48]. The primary purpose of the P and S nervous systems is to maintain homeostasis. As such, P&S measures are unique to the individual patient, documenting the patient’s individual responses to disease, therapy, and lifestyle in a way not available through any other measure. In this sense, P&S monitoring completes other measures. As an organ or system within the body starts to become dysfunctional, the P and S nervous systems work in concert to maintain homeostasis, regardless of the dysfunction [40]. Typically, early on, this compensates for the dysfunction, thereby delaying the onset of symptoms. That is the good news. Early P and S dysfunction (imbalance) signals the early (asymptomatic) end-organ dysfunction. The bad news is that the imbalance created by compensating for the organ’s dysfunction is asymptomatic. If prolonged, P&S imbalance (dysfunction) will induce secondary symptoms in other organ systems, causing additional comorbidities and increasing risk of mortality through accelerated autonomic decline. By the time patients present with symptoms, it is very late in the progression of decline and disease [25, 26]. Even so, establishing and maintaining proper P&S balance (function) for the individual patient reduces further morbidity and mortality [40]. However, it is even more efficient and, therefore, less costly to the patient and the nation to detect and treat the patient early to prevent the development of comorbidities and decrease the risk of mortality.

Chronic diseases, disorders, or injury lead to secondary symptoms. Secondary symptoms include hypertension secondary to autonomic dysfunction, dizziness (e.g., orthostatic hypotension), sleep difficulties, GI upset, urogenital dysfunction, and depression [25, 26]. If it were just diabetes that led to these comorbidities, then the disease process could be indicated. However, with many conditions leading to the same set of symptoms, it may be concluded that something else is involved. The commonality underlying all of these symptoms is the ANS (P and S nervous systems). Monitoring P and S function in the presence of chronic disease guides therapy for the individual patient, restoring autonomic balance (function), reducing the risk of morbidity, and therefore mortality, and reducing healthcare costs [24, 26].

The leadership recommends P&S monitoring as part of the standard of care for chronic diseases, such as those included herein, for this very reason. Again, early P and S dysfunction is asymptomatic but leads to more severely advanced autonomic dysfunctions and ultimately, autonomic neuropathy, then symptoms. Advanced autonomic dysfunction (including DAN) increases risk of morbidity. Autonomic neuropathy (CAN) is known to increase mortality risk. Together, they cause increases in medication load and hospitalizations, thereby increasing healthcare costs for the individual patient and the nation. Proper P&S balance, through application of lifestyle modifications or standard medications, regardless of time of application (including late in the progression of the disease and autonomic neuropathy) will minimize mortality and morbidity risk, reduce medication load and hospitalization, and reduce healthcare cost for the individual patient and the nation [44–48].

The effects of autonomic dysfunction, including autonomic neuropathy, transcend most fields of medicine, including internal medicine, cardiology, endocrinology, family medicine, general medicine, neurology, pulmonology, pain management, sleep medicine, and critical care. These examples will be discussed further below. In general, it is important to remember that P&S monitoring is not a treatment or therapy. P&S monitoring is a measurement highlighting P and S dysfunction regardless of the disease, disorder, or injury.

Independent, simultaneous P&S monitoring is a measurement, like a thermometer. Knowing that the thermometer works, we know that abnormal temperatures are a clinical risk. While there may be numerous causes for abnormal temperature, as well as numerous therapies and treatments, we know that we have to select therapies based on the diagnosed cause and the patient history. This may require additional testing to confirm the cause prior to prescribing the therapy. While the thermometer is not the cure, it documents the patient’s condition and follow-up temperature readings document the patient response to therapy and outcome.

Like the abnormal temperature, it is known that P and S dysfunction, including imbalance, increases risk of morbidity and mortality. It is known that restoring and maintaining proper P&S balance for the individual patient (like restoring normal temperature) reduces morbidity and mortality risk. It is known that P- and S-active medications and therapies (including beta-blockers, antihypertensives, antidepressants, bronchodilators, and vasopressors), when properly titrated for the patient, may restore P&S balance. Follow-up P&S testing documents patient responses to these frequently used therapies and detects early any asymptomatic changes in P&S activity that may return the risk of morbidity and mortality. P&S monitoring provides more information to guide therapy and document patient outcomes, thereby reducing medication load and hospitalizations and reducing healthcare costs, all while improving patient care.

Furthermore, just like the thermometer, restoring normal temperature does not necessarily relieve the disease or disorder. It does, however, stabilize the patient, minimizing morbidity risk. Restoring and maintaining normal P&S balance (such as with the medications listed above), barring end-organ effects, restores proper P and S control of the systems of the body. P and S dysfunction precedes symptoms. Symptoms are not demonstrated until end-organ effects, and it is the function of the PSNS and SNS to maintain normal end-organ function, even if the P and S themselves are dysfunctional. Therefore, it is important to monitor the PSNS and SNS frequently and periodically to enable restoration prior to end-organ dysfunction. What remains after restoration of P&S balance is specific to the dysfunctional organ or system itself, thereby enabling the physician to be more aggressive in treating the dysfunctional organ or system.

Independent, simultaneous P&S monitoring facilitates specifying and documenting P&S function, not only at rest but also the dynamic changes in response to challenges, including the actual challenge itself, not just the steady-state change that may be caused by the challenge. In 15.5 min, in the office, P&S monitoring (see Chap. 5) simulates and provides information similar to that from both Holter monitoring and tilt-table testing.

The five minute resting baseline documents patient-specific P&S balance and patient responses to disease, therapy, lifestyle, and genetics. P&S balance is computed as the ratio of S to P activity. The resting baseline also documents whether a patient demonstrates CAN, even while it is still asymptomatic. CAN is measured as very low resting parasympathetic activity (RFa < 0.1 bpm²), perhaps too low to prevent ventricular tachyrhythms from becoming fibrillation or worse. The resting baseline challenge highlights mortality risk.

The breathing challenges (DB and Valsalva) are early indicators of autonomic dysfunction or disease states. Example of disease states include pulmonary or upper respiratory disorders from the DB challenge and hypertension, pain, anxiety, or sleep apnea from the Valsalva challenge.

The five minute PC (stand) challenge completes the tilt-study simulation [8], helping to detect, differentiate, and document P&S involvement underlying syncope and orthostasis (including their subforms), and arrhythmia, any or all of which underlie dizziness, lightheadedness, or “vertigo.” While this is important, from an autonomic perspective, the stand challenge highlights the coordination between the P and S nervous systems. A lack of coordination (a type of dynamic balance) underlies or leads to increased morbidity, of which dizziness or lightheadedness is only one type of morbidity.

From the physicians’ perspective, there are several important issues for which P&S assessment offers additional information. This additional information guides therapy for the individual patient, reduces morbidity and mortality, improves patient outcomes, and reduces healthcare costs for the patient and the nation [20, 26, 41, 44–47, 49].

More information from P&S monitoring enables the measurement and documentation of patients’ individual responses to therapy, treatment, disease, lifestyle, genetics, injury, and disorder. As a result, physicians may improve therapy titration by titrating against an objective physiologic measure specific to the individual patient [6, 24, 26].

More information from P&S monitoring augments many of the ancillary tests currently ordered and performed. Since the P and S nervous systems control and coordinate all bodily functions [50–52], P&S assessment in conjunction with other ancillary tests provides even more information. Again, more information improves outcomes by enabling improved differentiation of the underlying causes of an individual patient’s symptoms. More information completes the requirements of evidence- and value-based medicine and comparative effectiveness benefit. Many tests, like EKG, Holter, stress tests, tilt studies, vascular studies, pulmonary function tests, bronchial studies, GI studies (both upper and lower), endocrine studies, bladder control studies, and bowel control studies, all measure cardiac or smooth muscle activity (see Appendix 3 for some examples). While these tests are important, they do not provide the “complete picture” that fully differentiates an individual patient.