Overview

The purpose of this protocol is to create an active natural history cohort of patients with degenerative movement disorders, tracked in a clinical setting with clinical rating scales and neuroimaging. The overarching rationale is that neurodegenerative diseases may be heterogeneous, complex disorders. A new way of performing clinical trials in these patients may be in order and this protocol aims to build a longitudinally tracked clinical trial-ready cohort of patients. The purpose of this protocol is to establish an active natural history cohort of patients with neurodegenerative movement disorders who are deeply phenotyped and "clinical trial ready" across Mass General Brigham.

After a thorough clinical diagnostic evaluation (this may include clinically indicated testing, for example MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, inflammatory tests, skin biopsy) the investigators aim to achieve this

through

1. Longitudinal tracking of clinical progression through use of clinical scales including at the present time: UMSARS, BARS, MoCA and UPSIT, PROM, MDS-NMS, UPDRS, and SARA
2. Longitudinal tracking of disease progression through use of neuroimaging including at the present time: TSPO-PET and 3D MRI (see section 1.3)

This is a pilot study designed to track patients with neurodegenerative movement disorders across Mass General Brigham through MRI and PET imaging modalities and clinical measures. Figure 5 represents the study design in detail. In short, subjects will be asked to visit Mass General Brigham every 6-9 months over the course of 18 months for imaging and clinical evaluation.

Eligibility

Inclusion Criteria:

1. Clinical diagnosis of neurodegenerative movement disorder by consensus criteria including: MSA, ataxias, synuclein duplication, atypical parkinsonism
2. Male and female subjects aged 18 and up

Exclusion Criteria:

1. Individuals with a known alternate neurologic disorder including: idiopathic PD, DLB, PSP, ALS, Alzheimer's, prion disease, frontotemporal dementia, seizure disorder, stroke, or brain tumor
2. Individuals with a previous head injury (with 15 minutes or greater loss of consciousness within the past 20 years)
3. Individuals with substance abuse, or substance abuse disorder
4. Brain MRI indicative of a significant abnormality (i.e. prior hemorrhage or infarct greater than 1 cm3, 3 or more lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space- occupying lesion).
5. Individuals with bipolar disease and schizophrenia
6. Concurrent medical conditions that contraindicate study procedures
7. Women who are pregnant, nursing, or seeking to become pregnant
8. Individuals with claustrophobia
9. Non-MRI compatible implanted devices
10. Corticosteroid treatment in the past four weeks
11. Low affinity binders to TSPO
12. Significant cognitive impairment (MoCA score ≤ 23) or poor understanding of study design