MRI Study Looking at Resting Brain Activity in Healthy Adults and Individuals With Parkinsonism and Rapid Eye Movement Disorder.

This proposal outlines a research plan that is focused on developing a reliable, valid, and reproducible imaging technique and statistical methodology for segregation of various forms of Parkinsonism, early diagnosis of Parkinsonism, and evaluation of how discrete behaviors might impact the measurement tools. The purpose of this protocol is to gather a multi-modal dataset to explore and validate the investigator's previous research findings in prior studies.

Subjects with PD, MSA-P, ET, or PSP will be recruited based on clinical criteria from the UAB Comprehensive Parkinson Disease and Movement Disorder Clinic located at The Kirklin Clinic at UAB. This center sees over 3,500 patients annually. Individuals with RBD will be recruited from the UAB University Hospital and UAB Highlands Sleep Disorders Center and will be identified through patient contact with a UAB Department of Neurology physician.

• Movement Disorders (Incl Parkinsonism)
• Tremor Familial Essential, 1
• REM Sleep Behavior Disorder

• Parkinson's Disease cohort
• Essential Tremor cohort
• Rapid Eye Movement Disorder Cohort
• Healthy Control group
• Supra Nuclear Palsy
• Parkinsonism - Undifferentiated

Inclusion Criteria:

• Healthy Control • Age 35-85

Parkinson Disease (PD) Age 35-85

Diagnosis of clinically definite PD made by a movement disorders specialist, with clinical evidence from chart review or documentation by referring physician of the following features:

• Presence of bradykinesia and 1 or both of the following:

  1. Rest tremor
  2. Rigidity
• Asymmetric Onset
• Progressive motor symptoms
• Levodopa responsive
• Duration at least 1 but not more than 10 years
• Hoehn and Yahr Stage 1-2

Progressive Supranuclear Palsy (PSP) Age 40-85

Diagnosis of clinically definite PSP made by a movement disorders specialist, with clinical evidence from chart review or documentation by referring physician of the following features:

• Gradually progressive disorder.
• Onset at age 40 or later.
• Vertical (upward or downward gaze) supranuclear palsy* and prominent postural instability with falls in the first year of disease onset*.
• No evidence of other disease that could explain the foregoing features, as indicated by mandatory exclusion criteria.

Parkinsonism of Other or Undetermined Cause (POC) Age 35-85

Diagnosis of parkinsonism of undetermined other other cause by a movement disorders specialist, with the following features documented on chart review or by the referring physician:

• Signs and symptoms of Parkinsonism including

  1. Bradykinesia
  2. Mixed or resting tremor
  3. Rigidity

  4. Characteristic deficits of gait and balance associated with Parkinsonism, including motor freezing or postural instability

     Essential Tremor (ET) Age 35-85

     Diagnosis of essential tremor by a movement disorders specialist, with the following features documented on chart review or by the referring physician:

• On examination, a 2+ postural tremor of at least 1 arm (a head tremor may also be present, but is not sufficient for the diagnosis)

• On examination, there must be

  1. a 2+ kinetic tremor during at least 4 tasks, or;
  2. a 2+ kinetic tremor on 1 task and a 3+ kinetic tremor on a second task; tasks include pouring water, using a spoon to drink water, drinking water, finger-to-nose, and drawing a spiral
• If on examination, the tremor is present in the dominant hand, then by report, it must interfere with at least 1 activity of daily living (eating, drinking, writing, or using the hands). If on examination, the tremor is not present in the dominant hand, then this criterion is irrelevant

REM Behavior Disorder (RBD) Age 25 - 85

Documented diagnosis of REM sleep behavior disorder (RBD) by a sleep medicine specialist, with the following documented clinical features on chart review or by a referring physician:

• Presence of REM sleep without atonia (RSWA) on polysomnography (PSG)

• At least one of the following conditions:

  1. Sleep-related, injurious, potentially injurious, or disruptive behaviors by history (eg, dream enactment behavior)
  2. Abnormal REM sleep behavior documented during PSG monitoring

Exclusion Criteria:

Healthy Control

• Known pregnancy
• Positive response to more than 3 items on the PD Screening Questionnaire
• Any first-degree blood relative affected by PD
• History of neurodegenerative disease
• History of repeated head injury
• History of encephalitis
• History of Brain Surgery
• History of Stroke
• History of dementia
• Active treatment with a neuroleptic
• Serious medical illness or comorbidity that may interfere with study participation

Parkinson Disease (PD)

• Any exclusion criteria that would exclude a healthy control patient

• Atypical features indicative of a Parkinson-Plus disorder such as Progressive Supranuclear Palsy (PSP), Multiple Systems Atrophy (MSA), or Corticobasal Degeneration (CBD), including:

  1. Cerebellar Signs
  2. Supranuclear Gaze Palsy
  3. Apraxia or other Cortical Signs
  4. Prominent Autonomic Failure
• Neuroleptic treatment at the time of onset of parkinsonism
• Active treatment with neuroleptic at time of study entry
• History of repeated strokes or stepwise progression of parkinsonism
• History of repeated head injury
• Definitive history of encephalitis
• Prominent early gait imbalance (<5 years)
• Dementia
• Hematologic malignancy or coagulopathy
• Known severe anemia (hct < 30)
• Known Pregnancy
• Brain surgery for Parkinsonism

Progressive Supranuclear Palsy (PSP)

• Any exclusion criteria that would exclude a healthy control patient
• Recent history of encephalitis.
• Alien limb syndrome, cortical sensory deficits, focal frontal or temporoparietal atrophy.
• Hallucinations or delusions unrelated to dopaminergic therapy.
• Cortical dementia of Alzheimer's type (severe amnesia and aphasia or agnosia, according to NINCDS-ADRA criteria).
• Prominent, early cerebellar symptoms or prominent, early unexplained dysautonomia (marked hypotension and urinary disturbances) .
• Severe, asymmetric parkinsonian signs (i.e. bradykinesia).
• Neuroradiologic evidence of relevant structural abnormality unrelated to appropriate changes known to be associated with PSP (for example, we would exclude those with basal ganglia or brain stem infarcts, or lobar atrophy on previous, non-research related imaging).

Parkinsonism of Other or Undetermined Cause (POC)

• Any exclusion criteria that would exclude a healthy control patient
• Signs and symptoms suggestive of clear diagnosis of idiopathic Parkinson disease, Progressive Supranuclear Palsy, or Essential Tremor (subjects in this case could be enrolled, but under a different diagnostic category, if they meet inclusion and exclusion criteria above)

Essential Tremor (ET)

• Any exclusion criteria that would exclude a healthy control patient
• Medications, alcohol, parkinsonism, dystonia, other basal ganglionic disorders, and hyperthyroidism are not potential etiologic factors for the tremor
• The tremor is not psychogenic (bizarre features, inconsistent in character,changing, subject is distractable, or other psychiatric features on examination
• Positive response to more than 3 items on the PD Screening Questionnaire
• Any first-degree blood relative affected by PD
• History of neurodegenerative disease

REM Behavior Disorder (RBD)

• Any exclusion criteria that would exclude a healthy control patient
• EEG epileptiform activity during REM sleep (unless RBD can be clearly distinguished from any concurrent REM sleep-related seizure disorder)
• Sleep disorder not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder