Enteric path study
|Principal Investigator: DavidShprecher|
|Keywords: parkinson's disease||Department: Neurology|
|IRB Number: 00056240||Co Investigator: KathleenBoynton|
|Specialty: Neurology, Neurology, Neurology|
|Sub Specialties: Movement Disorders, Parkinson's Disease, Sleep Disorders|
- Determine baseline clinical and enteric histopathologic characteristics of individuals enriched genetically (with strong family history) or clinically (with iRBD) for PD risk. 40 healthy controls, 20 iRBD, and 20 with strong PD family history will be enrolled. Hypothesis 1: The proportion of individuals with abnormal enteric alpha synuclein (a-syn) pathology is higher in at-risk populations than healthy controls.
- Determine the natural history of our at-risk study groups, over a 3-year period, using motor and non-motor (cognitive) measures. Hypothesis 2: New development of PD motor symptoms (parkinsonism), mild cognitive impairment, or dementia (determined by neuropsychological testing) will be observed at a higher rate in those with enteric a-syn pathology than those without.
- Measure resilience and progression of enteric histopathological findings in our study groups, using colon biopsies repeated after 3 years. Hypothesis 3: The proportion of individuals with enteric a-syn pathology will increase at a greater rate in at-risk study groups than in healthy controls.
Clinical inclusion/exclusion criteria: All participants will be at least 40 years of age. No individuals enrolled as healthy controls will have history, or clinical evidence, of a neurodegenerative or movement disorder. I will personally determine absence of these disorders with baseline measures outlined below. Individuals found to have dementia on baseline cognitive assessments will be excluded from participation.
Healthy controls without family history of PD will be matched for age, gender, and racial/ethnic background with participants from the following at-risk groups.
Healthy at-risk individuals with strong PD family history have at least two living individuals with first degree relationship to one another diagnosed with PD using United Kingdom Brain Bank (UKBB) criteria, as confirmed by the study PI.37 Once diagnosis is confirmed for both probands in a given family, then all PD patients and their first degree relatives are invited to participate.
All iRBD participants must meet 2005 International Classification of Sleep Disorders Diagnostic Criteria:38
A A. Presence of REM sleep without atonia: The EMG finding of excessive amounts of sustained or intermittent elevation of submental EMG tone or excessive phasic submental or (upper or lower) limb EMG twitching.
B. At least one of the following is present:
i. Sleep related injurious, potentially injurious, or disruptive behaviors by history.
ii. Abnormal REM sleep behaviors documented during polysomnographic monitoring.
C C. Absence of EEG epileptiform activity during REM sleep unless RSBD can be clearly distinguished from any concurrent REM sleep related seizure disorder.
D D. The sleep disturbance is not better explained by another sleep disorder, medical, or neurological disorder, mental disorder, medication use, or substance use disorder.
In order to document items B and C of the diagnostic criteria, individuals must have undergone a clinical sleep study (a standard of care procedure covered by medical insurance.) In addition to review of clinical records, I will personally confirm absence of a secondary cause for RBD. For item D, use of any medication with serotonin reuptake inhibiting (or serotonin receptor modulating) properties, in the prior 12 weeks, is an exclusion for subjects with RBD since this type of medication might precipitate this condition or at least REM sleep without atonia.
All female subjects: Since risks in pregnancy from sigmoidoscopy are unclear, women will be excluded from participation if they are pregnant (or expect to become pregnant during the period of study participation). A urine pregnancy test will be performed no more than one week prior to each research sigmoidoscopy. If the test is positive, the subject will not be able to undergo colon biopsy, and will need to end participation in the study. A pregnancy test will not be required for female participants who provide medical record documentation that they are surgically sterile (due to bilateral oophorectomy).
Healthy Controls: No individuals enrolled as healthy controls will have any have signs (based on history or examination) of a neurodegenerative or movement disorder.
RBD subjects: In addition to review of clinical records, PI will personally confirm absence of a secondary cause for RBD with history and neurologic examination. Use of any medication with serotonin reuptake inhibiting (or serotonin receptor modulating) properties, in the prior 12 weeks, is an exclusion for subjects with RBD since this type of medication might precipitate this condition or at least REM sleep without atonia.