Similar to diabetes, heart disease, and other chronic diseases, chronic progressive neurological diseases eventually involve (among other things) hypertension secondary to autonomic dysfunction, sleep and GI tract motility disturbances, and urogenital dysfunction. These are, at least in part, P&S-controlled quality of life functions. Parkinson’s disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) are in a class of neurodegenerative disorders called synucleinopathies. For example, PD is characterized by dopamine dysregulation. Dopamine is part of the cholinergic pathway (see section “Biochemistry” in Chap. 1). Therefore, dopamine-based PD therapy (e.g., levodopa) may be affecting the P and S directly as well as indirectly. Maintaining a proper P&S balance for the individual patient throughout the life of that patient helps to minimize morbidity and mortality risk, protecting quality of life and possible helping to preserve longevity. Regardless of the condition, earlier detection of P&S decline and restoration of balance, delays CAN onset and guides therapy to establish and maintain normal SB. These are the two main goals of P&S monitoring.

P and S involvement in PD, PAF, and MSA helps to differentiate them and helps to determine courses of treatment. Recent evidence suggests that there are two forms of PD: with and without orthostatic hypotension (OH). In fact, there is now debate over the reclassification of PD with OH as an ANS disease rather than a central NS (CNS) disease [1]. Based on new imaging techniques with 6-[18F]-fluorodopamine [2–4], Goldstein reports evidence for loss of sympathetic noradrenergic nerves in PD. Cardiac sympathetic denervation is virtually universal in patients with PD and neurogenic OH. About one-half of the patients with PD who do not have OH also have evidence for loss of noradrenergic innervation. The loss progresses over years, in a pattern suggesting “dying back.” Baroreflex–cardiovagal failure and cardiac sympathetic denervation often occur before onset of the movement disorder.

Denervation patterns similar to PD with OH are found in PAF patients. For patients with MSA, sympathetic innervation to the heart is preserved. It is known that early in the diseases process, PD and MSA are very similar in presentation. Further, it is known that PD therapy exacerbates MSA symptoms, if misdiagnosed. Often MSA patients are not responsive to levodopa (but not always) and often do not report dizziness (orthostatic abnormalities). However, orthostatic symptoms are easily masked or a result of medication or other disorders. P&S monitoring offers additional information that may help to discriminate the two disorders.

Patients with cardiac sympathetic denervation (PD with OH and PAF patients – collectively referred to as neurogenic OH patients) have an impaired inotropic response to sympathomimetics (e.g., tyramine). They failed to increase values for indices of cardiac contractility during IV tyramine infusion, whereas patients with neurogenic OH and intact cardiac innervation had normal inotropic responses. Patients with cardiac sympathetic denervation also had supersensitivities to beta-adrenergic agonists (e.g., isoproterenol). They had intact inotropic and chronotropic responses to the directly acting beta-adrenoceptor agonist. They were able to attain the target increment in HR (about 25 bpm). Patients with cardiac sympathetic denervation required lower doses of infused isoproterenol and had lower plasma isoproterenol concentrations than did patients with intact cardiac innervation. These findings suggest supersensitivity of cardiac adrenoceptor-mediated processes in denervated hearts. This pattern suggests that cardiac denervation is associated with decreased ability to release endogenous norepinephrine from sympathetic nerves and with supersensitivity of cardiac beta-adrenoreceptors. Failure to augment delivery of norepinephrine to its receptors may explain complaints such as fatigue and exercise intolerance in patients with cardiac sympathetic denervation in the setting of neurogenic OH [5].

MSA is due to central autonomic lesions and PAF is due to peripheral autonomic lesions. MSA entails loss of nigrostriatal neurons, decreased striatal 6-[18F]fluorodopa-derived radioactivity, and low cerebral spinal fluid levels of homovanillic acid. Most patients with MSA have neurogenic OH. In patients with PD and OH as an early, prominent disease manifestation, MSA is the favored diagnosis; however, in about 60 % of patients with PD and OH, orthostatic intolerance or hypotension develops before, concurrent with, or within 1 year after onset of the movement disorder. In response to therapy, the PD patient has a higher prevalence of levodopa responsiveness and positive family history of a neurodegenerative disease than did the MSA patient. The MSA patient has a higher prevalence of slurred speech and of erectile failure in men than the PD patient [6].

The imaging results for PD, MSA, and PAF have led some to indicate that the low-frequency (LFa, sympathetic) measure is more a measure of baroreceptor reflex modulation than of cardiac, sympathetic outflow [7, 8]. While this differentiation is important in very advanced cases (as typically seen in the neurocardiology unit at the NIH), the clinical differentiation is moot. The symptoms described and the therapies recommended, in the average patient, are the same whether the etiology is considered to be sympathetically mediated or BRR medicated, the latter, of course, itself being medicated by the sympathetics. In all other PD or MSA cases, clinically prescribed therapy is not different whether LFa is a measure of sympathetic outflow or of baroreceptor reflex. Beta-blockers and antihypertensives are still the recommendations to treat the hemodynamic symptoms of these neurological diseases.

Again, similar to diabetes, heart disease, and other chronic diseases, progressive, demyelinating, neurological diseases also eventually involve (among other things) hypertension secondary to autonomic dysfunction, sleep disturbances, dizziness, and GI tract motility and urogenital dysfunction. These are, at least in part, P&S-controlled quality of life functions. Maintaining a proper P&S balance for the individual patient throughout the life of the patient helps to minimize morbidity and mortality risk, protecting quality of life and possibly helping to preserve longevity. Regardless of the condition, earlier detection of P&S decline delays CAN onset and guides therapy to establish and maintain normal SB. These are the two main goals of P&S monitoring.

Autonomic dysfunction in patients with multiple sclerosis (MS) is associated with many signs and symptoms. It is generally reflected by bladder, bowel, sexual, and sweating dysfunctions and by abnormal response to autonomic tests. An abnormal response to standing, head-up tilt, cold-face test, the Valsalva maneuver, and DB has been reported in various studies. Patients with MS have significantly lower vagal responses during both unpaced and paced breathing conditions, as compared with control subjects. Patients also demonstrate abnormal cardiovascular regulation in heterogeneous patterns that are consistent with scattered plaques and lesions of the brainstem associated with autonomic function [9].