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We sought to evaluate overall survival (OS) and local recurrence (LR) in patients with grade 2 meningiomas treated with adjuvant radiotherapy compared to surgery alone at time of diagnosis. All patients at the authors' institution between 2007 and 2020 were retrospectively reviewed. OS, LR, and treatment toxicities were assessed. Sensitivity analyses were performed for patients with initial gross total resection (GTR) and subtotal resection (STR). Kaplan-Meier analyses and log-rank test for significance were used to compare surgery alone and adjuvant radiotherapy groups. We included 189 patients with mean age 57.4 ± 14.6 years. Patients were 64% female, and median follow-up was 64 (interquartile range: 20−96) months. At initial treatment, 21 patients received adjuvant radiotherapy and 168 received surgery alone. There was no significant difference for OS (hazard ratio = 1.3 [95% confidence interval 0.4−4.5], P = 0.92) overall or when limited to GTR (P = 0.38) or STR (P = 0.85). There was no significant difference in LR overall (P = 0.75) or when restricted to GTR (P = 0.77) or STR (P = 0.20). No patient had radiotherapy stopped or altered because of side effects; however, 71.4% reported tolerable side effects during the treatment period and 14.3% reported chronic side effects persisting longer than 12 months post treatment. In a large retrospective cohort, we found no survival or local recurrence benefit to adjuvant radiotherapy in treatment of grade 2 meningiomas. Sensitivity analysis limited to initial GTR and STR also failed to demonstrate any OS or LR benefit with adjuvant radiotherapy. In our experience, there is limited utility to upfront adjuvant radiotherapy following initial surgical resection in the treatment of grade 2 meningiomas. [ABSTRACT FROM AUTHOR]

Introduction: The clinical characteristics of Parkinson's disease (PD) associated with both the LRRK2 p.G2019S mutation and a GBA variant (LRRK2-GBA-PD) have not yet been determined.Methods: In this retrospective observational study of Ashkenazi-Jewish (AJ) PD patients, we describe the clinical course and characteristics of LRRK2-GBA-PD and estimate the risk to develop PD for the double mutation carriers. Odds ratios (OR) were estimated using published data on frequencies of GBA and LRRK2 mutations. Demographic and clinical data was retrieved from medical records and from rating at last visit.Results: Our analysis included 236 PD patients, divided into four groups: LRRK2-PD (n = 66), GBA-PD (n = 78), GBA-LRRK2-PD (n = 12) and mutation-negative PD (MNPD, n = 80 randomly selected). The estimated ORs in different models for GBA-LRRK2 PD were 15-28 (95% CI 6.7-72.0, p < 0.0001), compared to AJ controls. Using logistic regression (while controlling for sex, age at onset and PD duration), we found that probable REM-sleep behavior disorder (RBD) was significantly more common for GBA-PD than for LRRK2-PD, while none of the GBA-LRRK2-PD patients reported RBD. Dementia was significantly more common for GBA-PD than for the LRRK2-PD and MNPD. Psychosis was the most common for GBA-PD and least common for LRRK2-GBA-PD.Conclusions: While GBA-PD is characterized by higher rates of dementia, probable RBD and psychosis, it seems that compared to the other groups, these features are less common for LRRK2-GBA-PD. This may imply to a possible protective effect of LRRK2 p.G2019S mutation among GBA variant carriers. [ABSTRACT FROM AUTHOR]

Abstract Background Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered. Methods GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD patients and 662 AJ controls, from Israel and New York. Additional AJ control data (n = 3044) from the Inflammatory Bowel Disease Exome Portal was used. Results Full GBA sequencing increased the number of variants discovered by 17.4%, compared to targeted genotyping. An additional 17 PD patients were identified with GBA- associated PD. The p.E326K variant was found in 1.6% of AJ PD patients, making it the second most common PD-associated GBA variant in AJ. GBA variants were found in 18% of PD patients and 7.5% of controls (OR = 2.7, 95%CI = 1.9–3.8, p < 0.0001). Conclusion Without full sequencing of GBA , or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials. [ABSTRACT FROM AUTHOR]

Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson's disease and dementia with Lewy bodies. In the current study, we aimed to evaluate the role of SMPD1 variants in isolated rapid eye movement sleep behavior disorder (iRBD). SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1287 controls from European descent. Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD. [ABSTRACT FROM AUTHOR]