Objective: To describe the clinical outcomes of two unrelated patients with LRRK2-PD who experienced rapid neurologic decline following subthalamic nucleus deep brain stimulation (STN-DBS).

Background: Deep brain stimulation (DBS) is a well-established therapy for motor symptoms in advanced PD. Advances in genomic research are reshaping our understanding of PD pathophysiology and revealing significant genetic heterogeneity within the disease. To date, LRRK2-PD has been generally associated with good motor outcomes after DBS, but genetics has only recently been factored into DBS outcomes.

Method: We present two unrelated patients with different LRRK2 variants who underwent STN-DBS and both developed rapidly progressive unexplained refractory dysarthria, craniocervical dystonia, postural instability, and gait failure. Patient 1 is a 50-year-old male with a heterozygous pathogenic LRRK2 variant (H230R) who developed unexplained progressive craniocervical dystonia, dysarthria, gait instability, and falls three years after uncomplicated STN-DBS. Patient 2 is a 73-year-old male with a heterozygous G2019S LRRK2 variant who developed virtually the same symptoms (dystonia, dysarthria, gait failure) one year after STN-DBS.

Results: Two unrelated individuals with different LRRK2 variants who experienced poor outcomes after STN-DBS highlight the potential influence of LRRK2 variants on DBS efficacy.  To date, no other explanation for their poor outcomes has been identified including preoperative clinical characteristics, improper programming, lead placement, device malfunction, infection, hemorrhage, or other perioperative/postoperative complications.

Conclusion: Although the literature has not yet reported poor DBS outcomes associated with LRRK2, we aim to raise awareness of a novel potential risk.  LRRK2-PD represents approximately 1% of sporadic cases of PD and until genotyping is universal, genetic variants may remain unrecognized in the DBS population.  In addition, LRRK2-PD is known to be pathologically heterogenous and distinct from idiopathic PD.  Further study and routine genotyping of DBS candidates may help to define the influence of genotype on clinical outcomes.

References: Artusi CA, Dwivedi AK, Romagnolo A, Pal G, Kauffman M, Mata I, Patel D, Vizcarra JA, Duker A, Marsili L, Cheeran B, Woo D, Contarino MF, Verhagen L, Lopiano L, Espay AJ, Fasano A, Merola A. Association of Subthalamic Deep Brain Stimulation With Motor, Functional, and Pharmacologic Outcomes in Patients With Monogenic Parkinson Disease: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019 Feb 1;2(2):e187800. doi: 10.1001/jamanetworkopen.2018.7800. PMID: 30707228; PMCID: PMC6484599.

Prendes Fernández P, Blázquez Estrada M, Sol Álvarez J, Álvarez Martínez V, Suárez San Martín E, García Fernández C, Álvarez Carriles JC, Lozano Aragoneses B, Saiz Ayala A, Santamarta Liébana E, González Álvarez L. Analysis of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with monogenic PRKN and LRRK2 forms of Parkinson’s disease. Parkinsonism Relat Disord. 2023 Feb;107:105282. doi: 10.1016/j.parkreldis.2023.105282. Epub 2023 Jan 11. PMID: 36657280.

Asimakidou E, Xiromerisiou G, Sidiropoulos C. Motor and Non-motor Outcomes of Deep Brain Stimulation across the Genetic Panorama of Parkinson’s Disease: A Multi-Scale Meta-Analysis. Mov Disord Clin Pract. 2024 May;11(5):465-477. doi: 10.1002/mdc3.13994. Epub 2024 Feb 6. PMID: 38318989; PMCID: PMC11078493.

Poulopoulos M, Cortes E, Vonsattel JP, Fahn S, Waters C, Cote LJ, Moskowitz C, Honig LS, Clark LN, Marder KS, Alcalay RN. Clinical and pathological characteristics of LRRK2 G2019S patients with PD. J Mol Neurosci. 2012 May;47(1):139-43. doi: 10.1007/s12031-011-9696-y. Epub 2011 Dec 23. PMID: 22194196; PMCID: PMC3335886.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rapid-neurologic-decline-after-subthalamic-nucleus-deep-brain-stimulation-in-leucine-rich-repeat-kinase-2-parkinsons-disease-lrrk2-pd/