Inclusion Criteria:

Normal Controls:  Healthy volunteers of both genders will comprise the normal control group.

1. Must be 30-80 years of age.
2. Normal autonomic reflex screen and normal autonomic symptom profile.
3. Subject must be pain-free and in good health.

Parkinson's Disease (PD)

1. Presence of all 3 cardinal features of PD (resting tremor, bradykinesia, and rigidity).
2. The clinical signs must be asymmetric.
3. Must have some beneficial response to levodopa therapy.
4. The patient must be 30-80 years of age.
5. The patient must be willing and able to comply with study requirements and to give written informed consent.

Parkinson’s Disease with Autonomic Failure (PD_AF). Defined as fulfilling criteria for PD, as outlined above, and in addition:

1. OH ( ≥30 mmHg reduction in systolic blood pressure (SBP) with head-up tilt) is required.

Multiple System Atrophy (MSA)

1. Diagnosis of Probable MSA requirements:
   1. The presence of OH (fall in SBP ≥ 30 mmHg) or urinary incontinence (persistent involuntary partial or total bladder emptying, accompanied by erectile dysfunction [in men]) or both.
   2. Poorly levodopa-responsive Parkinsonism or cerebellar ataxia
2. Additional inclusion criteria:
   1. Presence of OH (30 mmHg reduction in SBP with head-up tilt) is required.
   2. The patient must be 30-80 years of age.
   3. The patient must be willing and able to comply with study requirements and to give written informed consent.
3. Diagnosis of Possible MSA requirements:  A sporadic, progressive, adult (>30 y)–onset disease characterized by:
   1. Parkinsonism (bradykinesia with rigidity, tremor, or postural instability) or
   2. A cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction) and
   3. At least one feature suggesting autonomic dysfunction (otherwise unexplained urinary urgency, frequency or incomplete bladder emptying, erectile dysfunction in males, or significant orthostatic blood pressure decline that does not meet the level required in probable MSA) and
   4. At least one of the additional features shown in the following:
      1. Possible MSA-P or MSA-C
         1. Babinski sign with hyperreflexia
         2. Stridor
      2. Possible MSA-P
         1. Rapidly progressive parkinsonism
         2. Poor response to levodopa
         3. Postural instability within 3 y of motor onset
         4. Gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
         5. Dysphagia within 5 y of motor onset
         6. Atrophy on MRI of putamen, middle cerebellar peduncle, pons, or cerebellum
         7. Hypometabolism on FDG-PET in putamen, brainstem, or cerebellum
      3. Possible MSA-C
         1. Parkinsonism (bradykinesia and rigidity)
         2. Atrophy on MRI of putamen, middle cerebellar peduncle, or pons
         3. Hypometabolism on FDG-PET in putamen
         4. Presynaptic nigrostriatal dopaminergic denervation on SPECT or PET

Dementia with Lewy bodies (DLB)

1. The diagnosis of clinically probable DLB requires progressive cognitive decline with two of the following:
   1. Fluctuating cognition or arousal
   2. Recurrent formed visual hallucinations
   3. Spontaneous parkinsonism

Exclusion Criteria:

Normal Controls

1. Pregnant or lactating females.
2. Allergy to sulfites (more frequent in asthmatic patients).  Presence of this condition would exclude the subject from the modified Oxford. Participation in the Valsalva maneuvers and head-up tilt would still be allowed.
3. Chronic illnesses or the presence of other conditions that potentially involve the CNS or affect autonomic testing. These include cardiac disease, congestive heart failure, recent (<6 months) myocardial infarct, severe anemia, diabetes mellitus, alcoholism, malignant neoplasms, amyloidosis, hypothyroidism, sympathectomy, cerebrovascular accidents, pheochromocytoma, thyrotoxicosis, occlusive vascular disease, and neurotoxins or neuroactive drug exposure.
4. Orthopedic problems or cardiopulmonary disease, sufficient to compromise mobility and activity of daily living.
5. Any known concurrent infection, liver or kidney disease.
6. History of electroconvulsive therapy.
7. Concomitant therapy with anticholinergic, sympathomimetic, α- or β-adrenergic antagonists or agonists, or other medication which could interfere with testing of autonomic function.
8. Use of methylphenidate, cinnarizine, reserpine, amphetamine or a MAO-A inhibitor within six months prior to the baseline visit.
9. Concurrent use of tricyclic antidepressants, maprotiline, mecamylamine, methyldopa, or monoamine oxidase (MAO) inhibitors, due to the potential for drug interaction with phenylephrine.

Parkinson's Disease (PD)

1. All those listed for normal controls with the exception of the presence of PD.
2. Parkinsonism due to drugs (including neuroleptics, a-methyldopa, reserpine, and metoclopramide).  Patients cannot have been on neuroleptics regularly at any time and none within the six months prior to the baseline visit.  Occasional use of a neuroleptic as an antiemetic in the past is allowed, but none can have been used within the six months prior to entry and not more than three doses within the year preceding the baseline visit.
3. Diseases with features of PD, e.g. progressive supranuclear palsy, essential tremor, multisystem atrophy, striatonigral degeneration, olivopontocerebellar atrophy, postencephalitic Parkinsonism.
4. Dementia (DSM-IV criteria - Amer. Psych. Assoc., 1994).  The score on the Mini-Mental State Examination must be >24.
5. History of stroke (diagnosed on clinical grounds as an acute deterioration of neurological function typical of a stroke; confirmatory CT or MRI evidence of stroke will be useful but not necessary).
6. History of brain surgery for Parkinson's disease.
7. History of structural brain disease.

Multiple system atrophy (MSA)

1. All those listed for normal controls with the exception of the presence of MSA.

Dementia with Lewy bodies (DLB)

1. All those listed for normal controls with the exception of the inclusion criteria for dementia with Lewy bodies.