Facilitating Diagnostics and Prognostics of Parkinsonian Syndromes Using Neuroimaging

Prior treatment

• All females of child-bearing potential, between the ages of 18-55, will be excluded from the study, unless they are confirmed to be not pregnant with a pregnancy test prior to scanning
• Have a history of drug, alcohol, or substance dependence or abuse within the last year, or prior prolonged history of dependence or abuse
• Recreational drug use in past six months
• Treatment with dopamine blockers or depleters in a time course consistent with drug induced parkinsonism
• Hallucinations not induced by drugs

Other illness

• Has a current clinically significant heart disease that poses a safety risk
• Has a current clinically significant infectious disease or a medical comorbidity which poses a safety risk
• Has a history of relevant severe drug allergy or hypersensitivity
• Currently undergoing chemotherapy or radiation for cancer
• Central nervous systems disease or brain injury that would preclude participation in this study
• Psychiatric or neurological disorder that would preclude participation in this study
• Severe disease progression such that participation in the imaging tests would be impossible or difficult
• Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
• Absence of an observable response to high dose levodopa despite moderate disease severity
• Expert considers a diagnosis of alternative syndrome more likely than PD
• Rapid progression of gait impairment requiring wheelchair within 5 years of onset
• Severe autonomic failure in the first 5 years
• Absence of any of the common non-motor features of PD despite 5 years of disease
• Family history of ataxia or parkinsonism
• Predominant, otherwise unexplained impairment of episodic memory, suggestive of AD (Alzheimer's disease)
• Predominant, otherwise unexplained autonomic failure, e.g., orthostatic hypotension (orthostatic reduction in blood pressure after 3 minutes standing \> 30 mm Hg systolic or \> 15 mm Hg diastolic), suggestive of multiple system atrophy or Lewy body disease
• Predominant, otherwise unexplained visual hallucinations or fluctuations in alertness, suggestive of dementia with Lewy bodies
• Predominant, otherwise unexplained multisegmental upper and lower motor neuron signs, suggestive of motor neuron disease (pure upper motor neuron signs are not an exclusion criterion)
• History of encephalitis
• Identifiable cause of postural instability, e.g., primary sensory deficit, vestibular dysfunction, severe spasticity, or lower motor neuron syndrome
  • Control subjects

Lab values

• Sudden onset or step-wise or rapid progression of symptoms, in conjunction with corresponding imaging or laboratory findings, suggestive of vascular etiology, autoimmune encephalitis, metabolic encephalopathies, or prion disease

Age

• Parkinsonian features restricted to the lower limbs for \> 3 years
• Onset after age 75 years

Other

• For Aims 1 and 2:
• Any contraindications to undergoing the multimodal imaging program
• This study will require constant clear communication throughout the duration of the study; therefore, non-English speakers will be excluded
• Right-handed finger amputees
• Cast on right hand or fingers at the time of enrollment
• Has clinically significant liver, kidney, lung, metabolic or hormone disturbances which pose safety risk
• Inability to keep or maintain research appointments
  • For Aim 1:
• Non-availability of a suitable matched participant in the alternate progression group (fast or slow)
  • For Aim 2:
  • PD subjects
• Unequivocal cerebellar abnormalities
• Downward vertical gaze limitation or slowing of downward saccades
• Complete absence of progression of motor symptoms over 5 years unless due to treatment
• Early bulbar dysfunction within the first 5 years since diagnosis
• Inspiratory respiratory dysfunction (stridor or frequent sighs)
• Recurrent falls (\>1 per year) because of impaired balance in the first 3 years
• Disproportionate dystonic anterocollis or hand contractures of hands or feet within 10 years
• Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor toe signs)
• Bilateral symmetric parkinsonism
  • MSA subjects
• Clinically significant neuropathy
• White matter lesions suggesting multiple sclerosis
  • PSP subjects
• Prominent appendicular ataxia
• In the investigator's opinion, an unsuitable candidate to serve as a control

• For Aim 1:
• Diagnosis of Parkinson disease
• Existence of sufficient clinical data from previous UTS Southwestern longitudinal study to determine progression rate (categorized as fast or slow)
• Availability of suitable matched participant in the alternate progression group (fast or slow)
• Willingness to participate in the imaging studies required for this study and to provide written informed consent
  • For Aim 2:
  • PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for PD.
• Duration of PD (since diagnosis) is \< 5 years
• Willing to participate in imaging and clinical scoring visits, and provide written informed consent
• Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move)
  • MSA subjects will be recruited in accordance with the Second Consensus Statement on Diagnosis of Multiple System Atrophy.
• Duration of MSA (since diagnosis) is \< 5 years
• Willing to participate in imaging and clinical scoring visits, and provide written informed consent
• Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move away during the study)
  • PSP subjects will be recruited in accordance with the MDS Criteria for Diagnosis of Progressive Supranuclear Palsy and must meet the designation of "probable PSP" for inclusion.
• Willing to participate in imaging and clinical scoring visits, and provide written informed consent
• Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move away during the study)
  • Control subjects will be recruited who meet the following criteria:
• Roughly age and sex matched with the subjects in the PD cohort
• No history or examination findings suggestive of any neurodegenerative disease
• Normal gait, balance, and eye movements for age
• No clinical evidence for symptomatic orthostatic hypotension
• Willing to participate in imaging and clinical scoring visits, and provide written informed consent
• Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move away during the study)