Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson's disease patients with GBA mutations

Mangone, Graziella; Bekadar, Samir; Cormier‐Dequaire, Florence; Tahiri, Khadija; Welaratne, Arlette; Czernecki, Virginie; Pineau, Fanny; Karachi, Carine; Castrioto, Anna; Durif, F.; Tranchant, Christine; Devos, David; Thobois, Stéphane; Meissner, Wassilios G.; Navarro, Maria Soledad; Cornu, Philippe; Lesage, Suzanne; Brice, Alexis; Welter, Marie Laure; Corvol, Jean‐Christophe; Benchetrit, Eve; Delaby, Laure; Berthet, Deborah; Danjou, Fabrice; Vidaihlet, Marie; Krack, Paul; Pélissier, Pierre; Morand, Dominique; Delaigue, Christine; Barun, Nadia; Anheim, Mathieu; Pleuvret, Marie; Destée, Alain; Defebvre, Luc; Moreau, Caroline; Simonin, C.; Ryckewaert, Gilles; Kreisler, Alexandre; Mutez, Eugénie; Carrière, Nicolas; Hopes, Lucie; Tard, Céline; Grolez, Guillaume; Dujardin, Kathy; Pécheux, N; Delliaux, Marie; Rolland, Anne‐Sophie; Broussolle, Emmanuel; Laurencin, Chloé; Tison, François; Burbaud, Pierre

doi:10.1016/j.parkreldis.2020.04.002

Cited by 36 publications

(39 citation statements)

References 32 publications

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“…After the diagnosis of PD, GBA -PD patients show an increased risk of cognitive decline ( 22 , 23 , 25 , 26 , 41 , 43 , 44 ), including those receiving deep brain stimulation surgery ( 45 , 46 ). Specific cognitive domains seem to be more affected, particularly in visual short-term memory ( 47 ).…”

Section: Genotype–phenotype Correlation With Clinical Profile In Gba -Parkinson Diseasementioning

confidence: 99%

Exploring the Genotype–Phenotype Correlation in GBA-Parkinson Disease: Clinical Aspects, Biomarkers, and Potential Modifiers

Menozzi

Schapira

2021

Front. Neurol.

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Variants in the glucocerebrosidase (GBA) gene are the most common genetic risk factor for Parkinson disease (PD). These include pathogenic variants causing Gaucher disease (GD) (divided into “severe,” “mild,” or “complex”—resulting from recombinant alleles—based on the phenotypic effects in GD) and “risk” variants, which are not associated with GD but nevertheless confer increased risk of PD. As a group, GBA-PD patients have more severe motor and nonmotor symptoms, faster disease progression, and reduced survival compared with noncarriers. However, different GBA variants impact variably on clinical phenotype. In the heterozygous state, “complex” and “severe” variants are associated with a more aggressive and rapidly progressive disease. Conversely, “mild” and “risk” variants portend a more benign course. Homozygous or compound heterozygous carriers usually display severe phenotypes, akin to heterozygous “complex” or “severe” variants carriers. This article reviews genotype–phenotype correlations in GBA-PD, focusing on clinical and nonclinical aspects (neuroimaging and biochemical markers), and explores other disease modifiers that deserve consideration in the characterization of these patients.

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Section: Genotype–phenotype Correlation With Clinical Profile In Gba -Parkinson Diseasementioning

confidence: 99%

Exploring the Genotype–Phenotype Correlation in GBA-Parkinson Disease: Clinical Aspects, Biomarkers, and Potential Modifiers

Menozzi

Schapira

2021

Front. Neurol.

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“…In heterozygous GBA PD, the first symptoms manifest 3–6 years earlier than in iPD, a rigid akinetic motor phenotype is more common, and the response to levodopa is good. However, at least in a subset of patients, the progression of the disease can be faster and therapeutic outcomes are often limited by earlier development of motor fluctuations and dyskinesias, as well as cognitive decline after DBS ( 114 , 115 ). GBA mutation carriers are also more likely to manifest non-motor symptoms.…”

Section: Introductionmentioning

confidence: 99%

Genotype-Phenotype Correlations in Monogenic Parkinson Disease: A Review on Clinical and Molecular Findings

et al. 2021

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Parkinson disease (PD) is a complex neurodegenerative disorder, usually with multifactorial etiology. It is characterized by prominent movement disorders and non-motor symptoms. Movement disorders commonly include bradykinesia, rigidity, and resting tremor. Non-motor symptoms can include behavior disorders, sleep disturbances, hyposmia, cognitive impairment, and depression. A fraction of PD cases instead is due to Parkinsonian conditions with Mendelian inheritance. The study of the genetic causes of these phenotypes has shed light onto common pathogenetic mechanisms underlying Parkinsonian conditions. Monogenic Parkinsonisms can present autosomal dominant, autosomal recessive, or even X-linked inheritance patterns. Clinical presentations vary from forms indistinguishable from idiopathic PD to severe childhood-onset conditions with other neurological signs. We provided a comprehensive description of each condition, discussing current knowledge on genotype-phenotype correlations. Despite the broad clinical spectrum and the many genes involved, the phenotype appears to be related to the disrupted cell function and inheritance pattern, and several assumptions about genotype-phenotype correlations can be made. The interest in these assumptions is not merely speculative, in the light of novel promising targeted therapies currently under development.

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“…Though alterations in the rate and pattern of basal ganglia neurons may partly explain the phenotypic variation (8), the contribution of individual genotype to differences in beta power has not yet been explored. This is important because an increasing number of studies have demonstrated that genotype is an important predictor of DBS outcome (9)(10)(11)(12)(13). For instance, several studies have shown that glucocerebrosidase (GBA) mutation carriers fare worse with STN-DBS compared with non-mutation carriers from a cognitive standpoint, though they still maintain motor benefit (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…This is important because an increasing number of studies have demonstrated that genotype is an important predictor of DBS outcome (9)(10)(11)(12)(13). For instance, several studies have shown that glucocerebrosidase (GBA) mutation carriers fare worse with STN-DBS compared with non-mutation carriers from a cognitive standpoint, though they still maintain motor benefit (9)(10)(11)(12)(13). In contrast, LRRK2 G2019S mutation carriers fare the same as non-mutation carriers from a cognitive standpoint and have at least the same or even better motor outcome compared with sporadic PD patients (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…For instance, several studies have shown that glucocerebrosidase (GBA) mutation carriers fare worse with STN-DBS compared with non-mutation carriers from a cognitive standpoint, though they still maintain motor benefit (9)(10)(11)(12)(13). In contrast, LRRK2 G2019S mutation carriers fare the same as non-mutation carriers from a cognitive standpoint and have at least the same or even better motor outcome compared with sporadic PD patients (9)(10)(11)(12)(13). Very importantly, 22-27% of individuals undergoing STN-DBS have a genetic form of PD (13,14), indicating that genetic variability could be particularly useful in understanding individual patient phenotype and DBS outcome.…”

Section: Introductionmentioning

confidence: 99%

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Subthalamic Peak Beta Ratio Is Asymmetric in Glucocerebrosidase Mutation Carriers With Parkinson's Disease: A Pilot Study

et al. 2021

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Introduction: Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). Glucocerebrosidase (GBA) mutation carriers, compared to sporadic PD, present with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non-GBA mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-GBA and GBA mutation carriers with PD.Materials and Methods: STN (left and right) resting state local field potentials were recorded intraoperatively from 4 GBA and 5 non-GBA patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity.Results: Peak beta ratio was significantly different between the left and the right STN for the GBA group (p < 0.01) but not the non-GBA group (p = 0.56) after co-varying for age, age of disease onset, and disease severity.Discussion: Peak beta ratio in GBA mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that GBA mutation carriers have a physiologic signature that is distinct from that found in sporadic PD.

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Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson's disease patients with GBA mutations

Cited by 36 publications

References 32 publications

Exploring the Genotype–Phenotype Correlation in GBA-Parkinson Disease: Clinical Aspects, Biomarkers, and Potential Modifiers

Exploring the Genotype–Phenotype Correlation in GBA-Parkinson Disease: Clinical Aspects, Biomarkers, and Potential Modifiers

Genotype-Phenotype Correlations in Monogenic Parkinson Disease: A Review on Clinical and Molecular Findings

Subthalamic Peak Beta Ratio Is Asymmetric in Glucocerebrosidase Mutation Carriers With Parkinson's Disease: A Pilot Study

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