Understanding dopaminergic dose reduction following STN-DBS: mediation analysis.
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Lanore Aymeric, Houot Marion, Basset Aymeric, Bendetowicz David, Menon Poornima J, Bardinet Eric, Fernandez Vidal Sara, Cornillault Jordan, Karachi Carine, Navarro Soledad, Ihle Jonas, Eusebio Alexandre, Giordana Caroline, Rouaud Tiphaine, Drapier Sophie, Guehl Dominique, Marques Ana, Hubsch Cécile, Jarraya Béchir, Benatru Isabelle, Thobois Stephane, Hopes Lucie, Maltete David, Rascol Olivier, Tir Melissa, Moreau Caroline, Tranchant Christine, Rolland Anne-Sophie, Devos David, Corvol Jean Christophe, Grabli David, Hainque Elodie, PREDISTIM study group
Аннотация
METHODS: Data from 144 patients treated by STN-DBS were analysed. Predictors of LEDD reduction were selected using the Boruta algorithm, a machine-learning method comparing variable importance to randomised features and then tested in a structural equation model for direct and motor-mediated effects.
RESULTS: Mean LEDD reduction was 41.7% (±38.2%) and motor improvement was 48.6% (±26.7%) at 1 year. Among the four predictors identified by Boruta, lower baseline LEDD (β=0.39, p=0.001), greater axial impairment (β=-0.25, p=0.003) and higher total volume of tissue activated (β=-0.17, p=0.031) were directly associated with lower LEDD reduction, independent of motor improvement. Sensorimotor STN overlap was not directly linked to LEDD reduction but was positively associated with motor improvement (β=0.34, p=0.001), which showed a trend-level effect on LEDD reduction (β=0.16, p=0.065). The total effect of sensorimotor STN overlap on LEDD reduction was not significant.
DISCUSSION: Dopaminergic dose reduction after STN-DBS is constrained by preoperative axial symptoms and stimulation spread, independently of motor improvement, while sensorimotor STN overlap improves motor symptoms but not dose reduction. Integrating motor phenotype with anatomical guidance may enhance medication management post DBS.