Genetic background and outcome of Deep Brain Stimulation in Parkinson's disease

Rizzone, Mario Giorgio; Martone, Tiziana; Balestrino, Roberta; Lopiano, Leonardo

doi:10.1016/j.parkreldis.2018.08.006

Cited by 35 publications

(34 citation statements)

References 62 publications

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“…We report the following key findings: (1) DBS outcome appears excellent in patients with LRRK2 p.G2019S (c.6055G > A) mutations, good in patients with PRKN mutations and poor in patients with LRRK2 p.R1441G (c.4321C > G) mutations, (2) the overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S (c.6091A > T) mutations may be decreased due to rapid progression of cognitive and neuropsychiatric symptoms, and (3) in other mutations, the motor outcome in DBS-treated genetic PD patients appears generally comparable to that of sporadic PD patients. A recent smaller review of 30 studies described the effects of DBS mainly in patients with LRRK2, PRKN and GBA mutations [62]. In the present PRISMA-compliant systematic review of 46 studies and 221 patients, the most comprehensive data were available for patients with LRRK2 and PRKN mutations.…”

Section: Discussionmentioning

confidence: 90%

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

et al. 2019

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Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5-10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common LRRK2 mutation, p.G2019S, and good in patients with PRKN mutations but poor in patients with the more rare LRRK2 p.R1441G mutation. The overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.

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Section: Discussionmentioning

confidence: 90%

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

et al. 2019

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“…Genetic testing provides the opportunity to correlate individual genotype with clinical outcome of therapies such as DBS [8]. Before this can be successfully implemented, it is important to understand patient knowledge and attitudes regarding genetic testing.…”

Section: Discussionmentioning

confidence: 99%

“…As genotype-phenotype correlations become more clear, it is possible that genetic mutation status may soon play a role in clinical decision-making for treatments and interventions such as DBS [8]. For instance, it has recently been reported that LRRK2 G2019S mutation carriers have greater improvement from DBS compared with nonmutation carriers [9].…”

Section: Introductionmentioning

confidence: 99%

Patient Knowledge and Attitudes towards Genetic Testing in Parkinson’s Disease Subjects with Deep Brain Stimulation

Fraint

Ouyang

Metman

et al. 2019

Parkinson's Disease

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Objectives. As genetic testing is becoming more widely commercially available for Parkinson’s disease (PD) and may have implications regarding clinical outcomes for deep brain stimulation (DBS) and other therapies, we aimed to determine patient knowledge and attitudes towards genetic testing. Methods. A sample of 88 PD subjects with bilateral STN-DBS completed a Genetic Attitudes Questionnaire (GAQ). Knowledge and attitudes towards genetic testing were assessed. Results. The mean percent of correct responses regarding genetic testing knowledge was 58.5%. Nearly 90% of subjects were unfamiliar with Genetic Information Nondiscrimination Act (GINA). The most important reasons subjects cited in deciding whether to undergo genetic testing included (1) to be a candidate for clinical trials if positive, (2) to learn that they do not carry a mutation, and (3) because a healthcare provider had recommended it. Individuals who influence decision-making include spouses and children. About 88% of subjects would share results with spouses, children, and siblings. Discussion. These results reveal that there is a major knowledge gap regarding genetic testing in PD and the implications of testing results on treatment, work, insurance, and privacy. Also, subjects would mainly seek genetic testing to participate in clinical trials, with spouses and children being the key stakeholders in decision-making.

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“…Case reports and small case‐control studies have reported the effects of DBS in different genetic forms of PD with heterogeneous measures. While the present study was underway, Rizzone and colleagues narratively described outcomes of DBS in PD‐related genes, Kuusimäki and colleagues systematically reviewed monogenic PD patients including subjective improvement as an outcome measure, and Artusi and colleagues quantitatively reported STN‐DBS outcomes in monogenic PD patients. None of these studies addressed motor outcome over time.…”

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confidence: 99%

Deep Brain Stimulation in Patients With Mutations in Parkinson's Disease–Related Genes: A Systematic Review

Oliveira

Barbosa

Aquino

et al. 2019

Movement Disord Clin Pract

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Background Background: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), and careful selection of candidates is a key component of successful therapy. Although it is recognized that factors such as age, disease duration, and levodopa responsiveness can influence outcomes, it is unclear whether genetic background should also serve as a parameter. Objectives Objectives: The aim of this systematic review is to explore studies that have evaluated DBS in patients with mutations in PD-related genes. Methods Methods: We performed a selective literature search for articles regarding the effects of DBS in autosomal dominant or recessive forms of PD or in PD patients with genetic risk factors. Data regarding changes in motor and nonmotor scores and the presence of adverse events after the stimulation were collected. ResultsResults: A total of 25 studies were included in the systematic review, comprising 135 patients. In the shorter term, most patients showed marked or satisfactory response to subthalamic DBS, although leucine rich repeat kinase 2 carriers of R114G mutations had higher rates of unsatisfactory outcome. Longer term follow-up data were scarce but suggested that motor benefit is sustained. Patients with the glucosidase beta acid (GBA) mutation showed higher rates of cognitive decline after surgery. Motor outcome was scarce for pallidal DBS. Few adverse events were reported. Conclusions Conclusions: Subthalamic DBS results in positive outcomes in the short term in patients with Parkin, GBA, and leucine-rich repeat kinase 2 (non-R144G) mutations, although the small sample size limits the interpretation of our findings. Longer and larger cohorts of follow-up, with broader nonmotor symptom evaluations will be necessary to better customize DBS therapy in this population.

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Genetic background and outcome of Deep Brain Stimulation in Parkinson's disease

Cited by 35 publications

References 62 publications

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

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

Patient Knowledge and Attitudes towards Genetic Testing in Parkinson’s Disease Subjects with Deep Brain Stimulation

Deep Brain Stimulation in Patients With Mutations in Parkinson's Disease–Related Genes: A Systematic Review

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