This study will conduct tests in patients with primary chronic autonomic failure (CAF) to learn more about these disorders, which include pure autonomic failure, multiple system atrophy, Parkinson's disease with autonomic failure, and autoimmune autonomic neuropathy.

Healthy volunteers and patients with primary CAF 18 years of age or older may be eligible for this study. Participants undergo some of the following tests:

• Blood studies, including arterial catheter insertion to measure blood pressure and collect arterial blood samples, blood flow studies using sensors applied to the skin and a pressure cuff around a limb, and blood draw for genetic studies.
• Bladder motility: Ultrasound test of bladder function.
• Electrocardiogram and heart ultrasound.
• Responses to changes in temperature: Warm water and then room temperature water are passed through watertight pads applied to the back and front of the body and body temperatures are measured.
• Gastrointestinal motility: Bowel sounds are recorded using a microphone placed on the abdomen.
• Lower body negative pressure: The lower body is placed into an airtight barrel-like chamber. Some air is sucked out of the barrel, causing blood to pool in the legs, as occurs during standing.
• Lumbar puncture: A needle is inserted in the space between the bones in the lower back to collect a small sample of cerebrospinal fluid.
• Microdialysis to measures levels of chemicals in the body fluid of certain tissues. A solution is passed through a thin tube inserted into the skin. Chemicals in the body tissues enter the solution. The solution is collected and the chemical levels are measured.
• PET scanning: A nuclear medicine test to produce images of body organs. For patients with urinary problems, a catheter is inserted into the bladder before starting the scan.
• Pupillometry: The pupil of the eye is measured using a special camera in a light-controlled room.
• QSART. A small amount of a brain chemical is applied to the skin with a tiny amount of electricity, and the sweat in a nearby patch of skin is measured.
• Measurement of saliva production, using a cotton-like material placed between the teeth and gums to absorb saliva.
• Skin electrical conduction test, using sensors on the skin to measure sweat production.
• Skin and core temperature measurements using sensors on the skin and in the ear canal.
• Speech and swallowing assessment for patients with speech and swallowing difficulties.
• Stress echocardiogram: A catheter is placed in the subject's arm for sampling blood or giving a drug while the subject exercises. During the test, blood pressure, pulse rate, and EKG are continuously monitored.

Objective: In dysautonomias, altered function of the autonomic nervous system adversely affects health. Primary abnormalities of autonomic function have been classified clinically into different chronic autonomic failure (CAF) syndromes. This protocol calls for comprehensive evaluation of autonomic function, using physiological, neuropharmacologic, neurochemical, and neuroimaging approaches, to identify lesion types and sites in CAF and improve the diagnosis and understanding of pathophysiologic mechanisms of CAF.

Study Population: The study population consists of patients with idiopathic, or primary, chronic autonomic failure (CAF). CAF syndromes include Parkinson disease with autonomic failure (manifested especially by neurogenic orthostatic hypotension, NOH), multiple system atrophy, and pure autonomic failure. Comparison groups include healthy volunteers and patients with Parkinson disease who do not have NOH.

Design: Subjects undergo multiple physiological, neuropharmacologic, neurochemical, and neuroimaging tests, to see if the results by different modalities agree, cross-validating each other and distinguishing different types of primary CAF.

Outcome Measures: Physiological outcome measures include hemodynamic responses to the Valsalva maneuver and orthostasis. Neuropharmacologic measures include hemodynamic and neurochemical responses to test drugs that probe specific components of the autonomic nervous system. Neurochemical measures include plasma and cerebrospinal fluid levels of catecholamines and related compounds. Neuroimaging measures include 6-[18F]fluorodopamine, 6-[18F]fluorodopa, and (13)N-ammonia positron emission tomographic scanning and magnetic resonance imaging.

• INCLUSION CRITERIA:

The subjects are patients with known or suspected primary CAF, based on referral information and confirmation of the clinical diagnosis at the intake evaluation. They are classified by results of the intake evaluation and then undergo comprehensive autonomic function testing.

Participation in this protocol is offered to people 18 years old or older, independently of gender, race, age, ethnicity, religion, or any other demographic or sociopolitical classifications.

Control patients have previously diagnosed PD or MSA without orthostatic hypotension, confirmed at the time of the intake evaluation.

EXCLUSION CRITERIA:

People younger than 18 years old are excluded. Advanced age does not constitute an exclusion criterion.

A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.

A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are hepatic or renal failure (defined by serum creatinine more than 1.5 g/dL), symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, and symptomatic coronary heart disease. A positive HIV test result does not necessarily exclude a patient from participating. Patients are excluded from further participation if the results of the intake evaluation lead to a diagnosis of a secondary form of CAF, such diabetic autonomic neuropathy. If a patient has a history of glaucoma, then an ophthalmology consult will be obtained, to determine whether exposure to any of the procedures or test drugs would place the patient at undue risk. If so, then the patient will be excluded from that part of the study.

A candidate subject is excluded if clinical considerations require that the patient continue treatment with a drug likely to interfere with the scientific results. An example would be treatment with a tricyclic antidepressant. Patients with known or suspected allergy or hypersensitivity to any test drug are excluded from receiving that drug. Patients who must take medications daily in the following categories may be excluded: anticoagulants, tricyclic antidepressants, barbiturates, aspirin, or acetaminophen. Subjects who must take aspirin daily will not undergo arterial catheterization; however, they may be allowed to participate in other aspects of the study. Patients unable to discontinue nicotine or alcohol temporarily are excluded. Patients are not to discontinue any medications before the patient or the patient's doctor discusses this with the Principal Investigator, Research Nurse, or Nurse Practitioner. . If it is decided that discontinuing medications would be unsafe, then the patient may be excluded from all or part of the study. Subjects must discontinue use of alcohol and tobacco throughout the period of testing in the protocol.

Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements must be discontinued before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.

Patients in whom we feel it would be difficult to insert a catheter into a vein are excluded. Subjects who are not expected clinically to tolerate lying still during the procedures are excluded.

Pregnant women are excluded from the Protocol overall. In women with child bearing potential, blood testing for pregnancy will be done with 24 hours before initial testing (except for obtaining the medical history and physical examination) or any testing involving radioactivity under the Protocol. Repeat pregnancy testing will be done before any procedure or drug administration under the Protocol that takes place more than one week from a previous pregnancy test.

Subjects may refuse certain tests or procedures, or may terminate participation early, without loss of benefits to which they were previously entitled. The Investigators may also exclude a subject from further participation, such as in the event of known or suspect falsification of medical history information or refusal to undergo planned tests or procedures, without loss of benefits to which the subject was previously entitled.