Neha Prakash1, Chelsea Caspell-Garcia2, Christopher Coffey3, Andrew Siderowf4, Caroline M Tanner5, Karl Kieburtz6, Brit Mollenhauer7, Douglas Galasko8, Kalpana Merchant9, Tatiana Foroud10, Lana M Chahine11, Daniel Weintraub12, Cindy Casaceli13, Ray Dorsey14, Renee Wilson15, Margaret Herzog16, Nichole Daegele17, Vanessa Arnedo18, Mark Frasier19, Todd Sherer20, Ken Marek21, Samuel Frank22, Danna Jennings23, Tanya Simuni24. 1. Northwestern University Feinberg School of Medicine, USA. Electronic address: neha.prakash@northwestern.edu. 2. The University of Iowa, USA. Electronic address: chelsea-caspell@uiowa.edu. 3. The University of Iowa, USA. Electronic address: christopher-coffey@uiowa.edu. 4. The University of Pennsylvania, USA. Electronic address: Andrew.siderowf@uphs.upenn.edu. 5. University of California San Francisco, USA. Electronic address: caroline.tanner@ucsf.edu. 6. University of Rochester Medical Center, USA. Electronic address: karl.kieburtz@chet.rochester.edu. 7. Center of Parkinsonism and Movement Disorders Paracelsus-Elena Klinik Kassel and University Medical Center Goettingen, Germany. Electronic address: brit.mollenhauer@med.uni-goettingen.de. 8. University of California San Diego, USA. Electronic address: dgalasko@ucsd.edu. 9. TransThera Consulting, USA. Electronic address: merchant.transthera@gmail.com. 10. Indiana University, USA. Electronic address: tforoud@iu.edu. 11. University of Pittsburgh, USA. Electronic address: lanachahine@pitt.edu. 12. The University of Pennsylvania, USA. Electronic address: daniel.weintraub@uphs.penn.edu. 13. University of Rochester Medical Center, USA. Electronic address: cindy.casaceli@chet.rochester.edu. 14. University of Rochester Medical Center, USA. Electronic address: ray.dorsey@chet.rochester.edu. 15. Clinical Trial Coordination Center, University of Rochester Medical Center, USA. Electronic address: renee.wilson@chet.rochester.edu. 16. Michael J Fox Foundation, USA. 17. Institute for Neurodegenerative Disorders, USA. Electronic address: ndaegele@invicro.com. 18. Michael J Fox Foundation, USA. Electronic address: varnedo@michaeljfox.org. 19. Michael J Fox Foundation, USA. Electronic address: mfrasier@michaeljfox.org. 20. Michael J Fox Foundation, USA. Electronic address: tsherer@michaeljfox.org. 21. Institute for Neurodegenerative Disorders, USA. Electronic address: kmarek@mnimaging.com. 22. Harvard Medical School, Beth Israel Deaconess Medical Center, Parkinson's Disease and Movement Disorders Center, Director of the HDSA Center of Excellence, USA. Electronic address: sfrank2@bidmc.harvard.edu. 23. Denali Therapeutics, USA. Electronic address: jennings@dnli.com. 24. Northwestern University Feinberg School of Medicine, USA. Electronic address: tsimuni@nmff.org.
Abstract
OBJECTIVE: To determine the feasibility, safety and tolerability of lumbar punctures (LPs) in research participants with early Parkinson disease (PD), subjects without evidence of dopaminergic deficiency (SWEDDs) and healthy volunteers (HC). BACKGROUND: Cerebrospinal fluid (CSF) analysis is becoming an essential part of the biomarkers discovery effort in PD with still limited data on safety and feasibility of serial LPs in PD participants. DESIGN/ METHODS: Parkinson's Progression Marker Initiative (PPMI) is a longitudinal observation study designed to identify PD progression biomarkers. All PPMI participants undergo LP at baseline, 6, 12 months and yearly thereafter. CSF collection is performed by a trained investigator using predominantly atraumatic needles. Adverse events (AEs) are monitored by phone one week after LP completion. We analyzed safety data from baseline LPs. RESULTS: PPMI enrolled 683 participants (423 PD/196 HC/64 SWEDDs) from 23 study sites. CSF was collected at baseline in 97.5% of participants, of whom 5.4% underwent collection under fluoroscopy. 23% participants reported any related AEs, 68% of all AE were mild while 5.6% were severe. The most common AEs were headaches (13%) and low back pain (6.5%) and both occurred more commonly in HC and SWEDDs compared to PD participants. Factors associated with higher incidence of AEs across the cohorts included female gender, younger age and use of traumatic needles with larger diameter. AEs largely did not impact compliance with the future LPs. CONCLUSIONS: LPs are safe and feasible in PD research participants. Specific LP techniques (needle type and gauge) may reduce the overall incidence of AEs.
OBJECTIVE: To determine the feasibility, safety and tolerability of lumbar punctures (LPs) in research participants with early Parkinson disease (PD), subjects without evidence of dopaminergic deficiency (SWEDDs) and healthy volunteers (HC). BACKGROUND: Cerebrospinal fluid (CSF) analysis is becoming an essential part of the biomarkers discovery effort in PD with still limited data on safety and feasibility of serial LPs in PD participants. DESIGN/ METHODS: Parkinson's Progression Marker Initiative (PPMI) is a longitudinal observation study designed to identify PD progression biomarkers. All PPMI participants undergo LP at baseline, 6, 12 months and yearly thereafter. CSF collection is performed by a trained investigator using predominantly atraumatic needles. Adverse events (AEs) are monitored by phone one week after LP completion. We analyzed safety data from baseline LPs. RESULTS: PPMI enrolled 683 participants (423 PD/196 HC/64 SWEDDs) from 23 study sites. CSF was collected at baseline in 97.5% of participants, of whom 5.4% underwent collection under fluoroscopy. 23% participants reported any related AEs, 68% of all AE were mild while 5.6% were severe. The most common AEs were headaches (13%) and low back pain (6.5%) and both occurred more commonly in HC and SWEDDs compared to PD participants. Factors associated with higher incidence of AEs across the cohorts included female gender, younger age and use of traumatic needles with larger diameter. AEs largely did not impact compliance with the future LPs. CONCLUSIONS: LPs are safe and feasible in PD research participants. Specific LP techniques (needle type and gauge) may reduce the overall incidence of AEs.
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