Dataset Information

Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI).

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.

SUBMITTER: Prakash N

PROVIDER: S-EPMC8978879 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI).

Prakash Neha N Caspell-Garcia Chelsea C Coffey Christopher C Siderowf Andrew A Tanner Caroline M CM Kieburtz Karl K Mollenhauer Brit B Galasko Douglas D Merchant Kalpana K Foroud Tatiana T Chahine Lana M LM Weintraub Daniel D Casaceli Cindy C Dorsey Ray R Wilson Renee R Herzog Margaret M Daegele Nichole N Arnedo Vanessa V Frasier Mark M Sherer Todd T Marek Ken K Frank Samuel S Jennings Danna D Simuni Tanya T

Parkinsonism & related disorders 20190131

<h4>Objective</h4>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).<h4>Background</h4>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.<h4>Design/methods</h4>Parkinson's Progressi ...[more]

PMID: 30738748

Similar Datasets

Project description:BackgroundThe Parkinson's Progression Markers Initiative (PPMI) is an ongoing observational, longitudinal cohort study of participants with Parkinson's disease, healthy controls, and carriers of the most common Parkinson's disease-related genetic mutations, which aims to define biomarkers of Parkinson's disease diagnosis and progression. All participants are assessed annually with a battery of motor and non-motor scales, 123-I Ioflupane dopamine transporter (DAT) imaging, and biological variables. We aimed to examine whether non-manifesting carriers of LRRK2 and GBA mutations have prodromal features of Parkinson's disease that correlate with reduced DAT binding.MethodsThis cross-sectional analysis is based on assessments done at enrolment in the subset of non-manifesting carriers of LRRK2 and GBA mutations enrolled into the PPMI study from 33 participating sites worldwide. The primary objective was to examine baseline clinical and DAT imaging characteristics in non-manifesting carriers with GBA and LRRK2 mutations compared with healthy controls. DAT deficit was defined as less than 65% of putamen striatal binding ratio expected for the individual's age. We used t tests, χ2 tests, and Fisher's exact tests to compare baseline demographics across groups. An inverse probability weighting method was applied to control for potential confounders such as age and sex. To account for multiple comparisons, we applied a family-wise error rate to each set of analyses. This study is registered with ClinicalTrials.gov, number NCT01141023.FindingsBetween Jan 1, 2014, and Jan 1, 2019, the study enrolled 208 LRRK2 (93% G2019S) and 184 GBA (96% N370S) non-manifesting carriers. Both groups were similar with respect to mean age, and about 60% were female. Of the 286 (73%) non-manifesting carriers that had DAT imaging results, 18 (11%) LRRK2 and four (3%) GBA non-manifesting carriers had a DAT deficit. Compared with healthy controls, both LRRK2 and GBA non-manifesting carriers had significantly increased mean scores on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (total score 4·6 [SD 4·4] healthy controls vs 8·4 [7·3] LRRK2 vs 9·5 [9·2] GBA, p<0·0001 for both comparisons) and the Scale for Outcomes for PD - autonomic function (5·8 [3·7] vs 8·1 [5·9] and 8·4 [6·0], p<0·0001 for both comparisons). There was no difference in daytime sleepiness, anxiety, depression, impulsive-compulsive disorders, blood pressure, urate, and rapid eye movement (REM) behaviour disorder scores. Hyposmia was significantly more common only in LRRK2 non-manifesting carriers (69 [36%] of 194 healthy controls vs 114 [55%] of 208 LRRK2 non-manifesting carriers; p=0·0003). Finally, GBA but not LRRK2 non-manifesting carriers showed increased DAT striatal binding ratios compared with healthy controls in the caudate (healthy controls 2·98 [SD 0·63] vs GBA 3·26 [0·63]; p<0·0001), putamen (2·15 [0·56] vs 2·48 [0·52]; p<0·0001), and striatum (2·56 [0·57] vs 2·87 [0·55]; p<0·0001).InterpretationOur data show evidence of subtle motor and non-motor signs of Parkinson's disease in non-manifesting carriers compared with healthy controls that can precede DAT deficit. Longitudinal data will be essential to confirm these findings and define the trajectory and predictors for development of Parkinson's disease.FundingMichael J Fox Foundation for Parkinson's Research.

Project description:BackgroundIdentifying a meaningful progression metric for Parkinson's disease (PD) that reflects heterogeneity remains a challenge.ObjectiveTo assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.MethodsUsing data from the Parkinson's Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains ("walking and balance"; "motor complications"; "cognition"; "autonomic dysfunction"; "functional dependence"; "activities of daily living"). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.ResultsHalf of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639).ConclusionClinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.

Dataset Information

Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI).

Objective

Background

Design/methods

Results

Conclusions

Publications

Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets