Progression and treatment of a series of patients with advanced LRRK2-associated Parkinson's disease

Abstract

Introduction: LRRK2 mutations have traditionally been associated with a benign phenotype of Parkinson's disease (PD). Favourable responses to deep brain stimulation (DBS) are reported in the advanced phase.

Methods: We performed a retrospective analysis of the clinical characteristics and progression of 13 patients with LRRK2-associated PD (13 with G2019S and 1 with I1371V). Nine patients were in the advanced phase, with a mean progression time of 7.2 years before reaching this phase.

Results: Seven patients underwent bilateral subthalamic DBS implantation, and 2 received infusion treatment. Patients with mutation G2019S responded excellently to DBS, with Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores improving by 80% at 6 months. This response was sustained over time. The patient with mutation I1371V had a severe phenotype of the disease, and presented a moderate response to DBS. Patients with advanced LRRK2-associated PD showed predominantly frontal cognitive involvement, with significant language impairment.

Conclusions: In these patients, progression was faster in the advanced stage of the disease. We emphasise the suitability of subthalamic DBS in the management of these patients.

Keywords: Advanced therapy; Deep brain stimulation; Enfermedad de Parkinson; Estimulación cerebral profunda; G2019S; LRRK2 mutations; Mutaciones LRRK2; Parkinson’s disease; Terapia avanzada.