Safety and Feasibility of Serial Lumbar Punctures: Long-term Results from the Parkinson’s Progression Markers Initiative
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Background and Objectives
The collection of cerebrospinal fluid (CSF) serves an essential role in biomarker research. New Parkinson’s disease (PD) classifications include CSF α-synuclein status as a key biological anchor to enrich research trial design. Previous reports have established the safety of lumbar punctures (LPs) at baseline, but further investigation of longitudinal LP feasibility is needed. This study aimed to evaluate the safety and feasibility of serial CSF collection in participants enrolled in the Parkinson’s Progression Markers Initiative (PPMI).
Methods
PPMI participants were evaluated over a 13-year period. Descriptive statistics were calculated for all scheduled LPs occurring annually from baseline through year five and biennially thereafter. Adverse events were examined for all participants who attempted at least one LP. Compliance, defined as percentage of LPs with CSF collection, was assessed at baseline and for each longitudinal follow up visit. Logistic regression and generalized linear mixed effects models were used to calculate odds ratios and 95% confidence intervals for predictors of baseline and longitudinal LP success.
Results
3479 participants enrolled in the PD (n=1412), prodromal (n=1768), and healthy control (n=299) cohorts were analyzed. 3360 participants attempted at least one LP of which 29.5% experienced an adverse event with 1.3% rated as severe. Compliance was 90% at baseline, 76.3% at year one, 67.8% at year three, 56.2% at year five, and 35.7% at year nine. From baseline to year five, percent change in compliance decreased by 39.4% in the PD cohort, 41.4% in the prodromal cohort, and 27.8% in the healthy control cohort. Predictive variables of baseline LP success included fewer years since diagnosis in the PD cohort (OR 0.82, 0.76-0.89), lower BMI in the prodromal cohort (OR 0.92, 0.89-0.94), and site location (U.S. vs. non-U.S.) for both PD (OR 1.5, 1.03-2.18) and healthy control (OR 3.6, 1.22-10.64) cohorts. Baseline LP success was the best predictor of longitudinal LP success (OR 7.82, 5.74-10.65).
Discussion
In this large study of longitudinal CSF collection, serial lumbar punctures were safe in PD research participants over a 13-year period. Although compliance was high over the first three years, further investigation is warranted to improve long term LP success.
