We thank Weill and colleagues for their valuable comments.1 Their observations corroborate our findings of cognitive decline post-DBS in PD patients carrying GBA mutations (GBA-PD) and they, like us, question the long-term risk-to-benefit of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in these patients. They caution, however, against a potential bias introduced by our use of non-operated GBA-PD patients accessed through the Parkinson’s Progression Marker’s Initiative (PPMI)2, as these patients may have had a milder clinical profile than the GBA-PD patients who underwent STN-DBS, and we acknowledge this limitation of our study. While it is correct that mean disease duration and follow-up time were both longer in the GBA-PD group with DBS compared with those without DBS, we statistically corrected for both factors and utilized two different techniques in our analysis, linear mixed modeling and propensity score weighting, both yielding similar results. Propensity score weighting is particularly useful to account for systematic differences between non-randomized groups in observational studies.3, 4 Even with their corroboration of our overall findings, we agree that further replication testing are needed, and only the use of prospective controlled studies would allow for definitive conclusions.
Currently, genetic testing for GBA mutations is not standard of care as part of the DBS pre-operative process, and the Weil et al. observations further support our recommendation that GBA testing and counseling be considered pre-operatively, if available. We do not claim that STN-DBS be categorically avoided in GBA-PD patients, rather approached cautiously, and GBA status may be a factor that is useful when considering the risk-benefit profile of STN-DBS. It remains to be explored whether treatments such as globus pallidus internus DBS (GPi-DBS) or other device-aided non-neurosurgical therapies result in better cognitive outcomes than STN-DBS in GBA-PD patients.5 Integrating GBA status into decision-making for DBS and potentially other device-aided therapies is likely to foster further studies of other genetic mutations on treatment outcomes as part of the overall effort to move towards precision medicine in PD.
Footnotes
Potential conflicts of interest: none.
References:
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