The LRRK2 G2019S mutation status does not affect the outcome of subthalamic stimulation in patients with Parkinson's disease

Greenbaum, Lior; Israeli‐Korn, Simon; Cohen, Oren S.; Elincx-Benizri, Sandra; Yahalom, Gilad; Kozlova, Evgenia; Strauss, Hanna; Molshatzki, Noa; Inzelberg, Rivka; Spiegelmann, Roberto; Israel, Zvi; Hassin‐Baer, Sharon

doi:10.1016/j.parkreldis.2013.07.005

Cited by 25 publications

(19 citation statements)

References 11 publications

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“…In 4 studies, the mean LEDD decreased from 17.5% to 75% as illustrated in Figure . Motor complications improved from 33.3% to 75% …”

Section: Resultsmentioning

confidence: 91%

“…The 25 articles included reported 151 patients with PD‐related mutations (2 patients are represented twice in Angeli and colleagues); from which 135 patients were included in the outcome analysis. The selected articles included PRKN , LRRK2 , Phosphatase and tensin homolog ( PTEN )‐induced putative kinase 1 ( PINK1 ), GBA , alpha‐synuclein ( SNCA ) and retromer complex component ( VPS35 ) mutations in addition to chromosome 22q11.2 microdeletion. Age at onset ranged from 10 to 57 years old, and the duration of disease at DBS implant ranged from 4 to 45 years .…”

Section: Resultsmentioning

confidence: 99%

“…From the 50 LRRK2 patients, 35 (70%) had shorter follow‐up data and 29 (58%) patients had intermediate follow‐up outcomes. The STN was the target in all patients.…”

Section: Resultsmentioning

confidence: 99%

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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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“…In 4 studies, the mean LEDD decreased from 17.5% to 75% as illustrated in Figure . Motor complications improved from 33.3% to 75% …”

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Seventeen studies [9,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] reported 87 patients (target: subthalamic nucleus (STN) n = 79, not available (NA) n = 8). The outcome was reported in 73 patients (83.9% of patients); with percentage improvement of the UPDRS-III score in 49 patients and verbally in 24 patients.…”

Section: Lrrk2mentioning

confidence: 99%

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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“…The leucine‐rich repeat kinase 2 ( LRRK2 ) G2019S mutation ( LRRK2 *G2019S) is the most common genetic mutation associated with PD . Parkinson's disease patients who are carriers of this mutation suffer from parkinsonism with clinical features indistinguishable from sporadic late onset idiopathic PD (IPD), and their response to medical and surgical treatment, rates of side effects, and complications are also similar to those manifested by sporadic, nonfamilial PD . Whether LRRK2 *G2019S associated‐PD and IPD are also indistinguishable in terms of disease progression is undtermined.…”

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confidence: 99%

Motor progression of Parkinson's disease with the leucine‐rich repeat kinase 2 G2019S mutation

et al. 2014

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The LRRK2 G2019S mutation status does not affect the outcome of subthalamic stimulation in patients with Parkinson's disease

Cited by 25 publications

References 11 publications

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

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

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

Motor progression of Parkinson's disease with the leucine‐rich repeat kinase 2 G2019S mutation

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