Objective: To compare the basal characteristics and postoperative clinical outcomes of LRRK2 mutation carriers and idiopathic Parkinson’s disease patients treated with subthalamic deep brain stimulation (STN-DBS).

Background: STN-DBS is a well-established treatment for patients with advanced Parkinson’s disease (PD). However, its long-term effects in monogenic PD are not well defined, especially for rare LRRK2 mutations like R1441G and I2020T.

Method: A single-center retrospective study comparing patients carrying LRRK2 mutations treated with STN-DBS and a cohort of idiopathic PD patients. Clinical data and scales were obtained from the medical records.

Results: Between 2015 and 2024, 15 patients with LRRK2 mutations (11 G2019S, 3 R1441G, 1 I2020T) underwent surgery, their outcomes were compared to a cohort of idiopathic PD patients. LRRK2-PD patients had earlier disease onset and underwent DBS at a younger age, with no difference in the time from disease onset to surgery. A higher proportion of LRRK2-PD had disabling dyskinesias as an indication for DBS (38.9% vs. 23.1%), without being statistically significant.

During postoperative follow-up, LRRK2-PD patients reported fewer cognitive symptoms (50% vs. 14%, p=0.03) and lower incidence of hallucinations/psychosis (5% vs. 23%, p=0.15). LRRK2-PD patients showed less reduction in UPDRS III (25% vs. 58%, p=0.03) and higher scores on post-surgical UPDRS IV at six months (8.8 vs. 1.3, p<0.01). They also exhibited a smaller reduction in LEDD and a higher number of daily medication doses at 6, 12, 36, and 60 months of follow-up, with these differences being sustained, though not reaching statistical significance (see Image 1). No differences were found in the number of therapeutic adjustments needed after DBS. However, two LRRK2-PD patients with refractory symptoms (disabling dyskinesia and dystonia) after 3 years of STN-DBS required additional advanced therapies: unilateral GPi-DBS and foslevodopa infusion, respectively.

Conclusion: All patients showed improvement with STN-DBS treatment, including those with R1441G mutations. LRRK2-PD patients were younger and received DBS at an earlier age. During follow-up, they reported less cognitive symptoms and a smaller reduction in total medication and daily doses. Notably, two patients required additional advanced treatments for refractory symptoms.

LEDD reduction and daily medication frecuency

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-outcomes-of-subthalamic-deep-brain-stimulation-in-lrrk2-patients/