Safety and Feasibility of Serial Lumbar Punctures: Long-term Results from the Parkinson's Progression Markers Initiative.

BACKGROUND

Cerebrospinal fluid (CSF) serves an essential role in biomarker research. New Parkinson's disease (PD) classifications incorporate CSF α-synuclein status into trial design. This study evaluated 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 13-years with lumbar punctures (LPs) occurring annually from baseline through year five and biennially thereafter. Adverse events and compliance, defined as percentage of LPs with CSF collection, were assessed at baseline and upon follow up. 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 (PD: n = 1412, prodromal: n = 1768, healthy control: n = 299) were analyzed. 3360 attempted at least one LP with 29.5 % experiencing an adverse event (1.3 % severe). Baseline compliance was 90 %. 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 (PD: OR 0.82, 0.76-0.89), lower BMI (prodromal: OR 0.92, 0.89-0.94), and site location U.S. vs. non-U.S. (PD: OR 1.5, 1.03-2.18, healthy control: OR 3.6, 1.22-10.64). Baseline LP success was the best predictor of longitudinal success (OR 7.82, 5.74-10.65).

CONCLUSIONS

Lumbar punctures were safe in PD research participants over a 13-year period. Compliance was high over the first three years, but further investigation is warranted to improve long term success.