Deep brain stimulation for monogenic Parkinson's disease: a systematic review

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Deep brain stimulation (DBS) is a key therapy for Parkinson's disease (PD) motor symptoms.
• Genetic factors influence PD, with mutations in LRRK2, PRKN, PINK1, SNCA, and GBA being common.
• Understanding genotype-specific DBS outcomes is crucial for personalized PD treatment.

Purpose of the Study:

• To systematically review the efficacy of DBS in patients with genetically defined Parkinson's disease.
• To analyze how different monogenic mutations affect DBS treatment outcomes.
• To identify genetic factors that may predict DBS response or compromise its benefits.

Main Methods:

• Systematic literature review of 46 studies.
• Inclusion of 221 patients with genetically characterized Parkinson's disease.
• Analysis of reported DBS effects stratified by specific gene mutations.

Main Results:

• DBS efficacy in monogenic PD varies significantly based on the causative gene mutation.
• Excellent outcomes observed in LRRK2 p.G2019S and good outcomes in PRKN mutations.
• Poor outcomes noted in LRRK2 p.R1441G mutations; potential compromise in SNCA, GBA, and LRRK2 p.T2031S due to cognitive/neuropsychiatric progression.

Conclusions:

• DBS response in Parkinson's disease is influenced by underlying genetic mutations.
• Specific mutations like LRRK2 p.G2019S and PRKN mutations are associated with favorable DBS outcomes.
• Cognitive and neuropsychiatric symptoms in certain genetic PD forms may limit overall DBS benefit.